Biomedical subjects

Stefan C Müller

Publications and source records attributed to Stefan C Müller.

At least 19 recordsLinked to original sources

PubMed2006

Excitation-induced dynamics of external pH pattern in Chara corallina cells and its dependence on external calcium concentration.

The influence of cell excitation and external calcium level on the dynamics of light-induced pH bands along the length of Chara corallina cells is studied in the present paper. Generation of an action potential (AP) transiently quenched these pH patterns, which was more pronounced at 0.05-0.1 mM Ca2+ than at higher concentrations of Ca2+ (0.6-2 mM) in the medium. After transient smoothing of the pH bands, some alkaline peaks reemerged at slightly shifted positions in media with low Ca2+ concentrations, while at high Ca2+ concentrations, the alkaline spots reappeared exactly at their initial positions. This Ca2+ dependency has been revealed by both digital imaging and pH microelectrodes. The stabilizing effect of external Ca2+ on the locations of recovering alkaline peaks is supposedly due to formation of a physically heterogeneous environment around the cell owing to precipitation of CaCO3 in the alkaline zones at high Ca2+ during illumination. The elevation of local pH by dissolving CaCO3 facilitates the reappearance of alkaline spots at their initial locations after temporal suppression caused by cell excitation. At low Ca2+ concentrations, when the solubility product of CaCO3 is not attained, the alkaline peaks are not stabilized by CaCO3 dissolution and may appear at random locations.

Calcium↗

PubMed2006

Prognostic value of CpG island hypermethylation at PTGS2, RAR-beta, EDNRB, and other gene loci in patients undergoing radical prostatectomy.

OBJECTIVES: To evaluate CpG island hypermethylation in a set of candidate genes in prostate cancer (pCA) and its relationship to clinicopathologic parameters and a nomogram predicting prostate-specific antigen (PSA) recurrence after radical prostatectomy. MATERIALS AND METHODS: Tissues of 78 prostate carcinomas, 32 benign prostate hyperplasias (BPHs), and prostate cell lines (LNCaP, DU145, PC3, BPH-1) were examined with MethyLight polymerase chain reaction at 13 gene loci (APC, CDC6, CTNNB1, E-Cadherin, EDNRB, FGFR2, GSTP1, NAB2, PKCmu, PTGS2, RAR-beta, RASL11A, WWOX). RESULTS: APC, RAR-beta, PTGS2, GSTP1, EDNRB, and CTNNB1 (83%, 71%, 65%, 33%, 14%, 9%, respectively) were methylated in pCA but rarely or not methylated in BPH. NAB2 and CDC6 were hypermethylated frequently in pCA (92%, 67%, respectively) and in BPH (91%, 59%, respectively). FGFR2, WWOX, E-Cadherin, PKCmu, and RASLL1A did not display noteworthy methylation in pCA (0-1%) or in BPH. CpG island hypermethylation at APC, retinoic acid receptor beta (RAR-beta), and PTGS2 discriminated with a sensitivity of 65-83% and a specificity of 97-100% between BPH and pCA. The combination of various genes increased the diagnostic expressiveness. PTGS2 hypermethylation correlated with seminal vesicle infiltration (p=0.047), capsular penetration (p=0.004), and pT stage (p=0.014). RAR-beta methylation was accompanied by a higher cumulative Gleason score (p=0.042). The probability of PSA-free-survival calculated with a Kattan nomogram correlated inversely with CpG island hypermethylation at EDNRB, RAR-beta, and PTGS2. All prostate cancer cell lines displayed a varying degree of demethylation after 5-aza-2'deoxycytidine treatment. CONCLUSIONS: CpG island hypermethylation at various gene loci is frequent in prostate cancer and can distinguish between neoplastic and noncancerous tissue. Furthermore, hypermethylation at PTGS2, RAR-beta, and EDNRB inversely correlated with PSA-free-survival according to a Kattan nomogram and has potential prognostic value.

Aged↗

PubMed2006

Desensitization effects in the ruthenium-catalyzed Belousov-Zhabotinsky reaction.

The influence of visible light on the velocities of spiral waves in the [Ru(bpy)](3)(2+) -catalyzed Belousov-Zhabotinsky (BZ) reaction is well documented. However, there are only few reports showing the effect of the way a change in the applied intensity is made, or on "desensitization" or "memory" type phenomena. In this paper, we present observations showing significant changes in spiral tip dynamics without varying the light intensity during the course of the experiments. We produce further evidence showing that changes in wave velocity and inhibitory effects are depending on whether the increase in intensity is applied in one large step or in a number of smaller steps. Also, the tip trajectories before and after the spiral waves have been subjected to an increase and subsequent decrease in intensity levels are different, suggesting a change in excitation of the system. The experimental results are separated into two groups depending on the light sensitivity of the system and the behavior of the spiral tip. Simulation results demonstrate that the different tip trajectories observed in the experiments can be modeled by only varying the excitation threshold. Our observations indicate that there must be at least two different competing pathways for the reaction mechanism not only in the oscillatory BZ system but also in excitable media and that intermediates may also play an important part in determining the excitation of the system and not just the initial concentrations of the reactants.

Journal Article↗

PubMed2006

An elegant method to study an isolated spiral wave in a thin layer of a batch Belousov-Zhabotinsky reaction under oxygen-free conditions.

A method to prepare a uniform thin layer of a batch Belousov-Zhabotinsky (BZ) reaction under oxygen-free conditions for the study of an isolated spiral wave is presented. After a first layer of gel soaked with the BZ solution has been delivered into the reactor, a single spiral wave was initiated, and finally the remaining reactor volume was filled with gel and BZ medium. The completely filled reactor is sealed gas-tightly, yielding oxygen-free, and thus more controlled, reaction conditions. A systematic study of the behaviour of an isolated spiral wave in a ferroin-catalyzed BZ reaction under batch conditions has been performed. Recipes for BZ media that support a slowly rotating meandering spiral were developed. In cases of extremely low excitability (i.e., relative large stimuli are required to induce a propagating wave), the number of petals in the trajectory of a spiral tip decreased due to aging of the reaction system. Since oxygen-free conditions are necessary for the study of the dynamics in three-dimensional excitable media, and the wave velocities of a spiral are sufficiently low, the developed chemical recipes are suitable for studies of the behaviour of scroll waves in three-dimensional systems by optical tomography.

Anaerobiosis↗

PubMed2006

Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis in urologic malignancies.

OBJECTIVES: Peripheral primitive neuroectodermal tumor (PNET) is a highly aggressive neoplasm belonging to the Ewing family of tumors. It is characterized by the expression of MIC2 and neural markers (eg, neuron-specific enolase, synaptophysin, S-100, vimentin, Leu-7), and the presence of the EWS-FLI1 translocation. METHODS: We performed a MEDLINE search for PNET in urologic malignancies. Additionally, we report on 2 cases of renal and 1 case of bladder PNET. The data obtained by reviewing patients with renal PNET were analyzed using Kaplan-Meier analysis. RESULTS: Renal PNET is diagnosed in young adults (median age 24 years). In contrast, the incidence of bladder PNET seems to be dependent on a defective immune mechanism. Patients often present with pain (84%), palpable tumor (60%), and hematuria (38%). The radiologic findings are uncharacteristic; therefore, the diagnosis should be based on the histologic and immunohistochemistry findings. Renal and bladder PNET are both often diagnosed at an advanced stage and, therefore, the prognosis is poor, despite aggressive multimodal treatment (surgery, polychemotherapy, radiotherapy). We identified palpable tumor masses (log-rank test, P = 0.0027) and synaptophysin expression (log-rank test, P = 0.0422) as prognostic unfavorable markers for renal PNET. CONCLUSIONS: Renal PNET should be considered in young patients who present with the classic triad of renal cancer, hematuria, and pain and palpable tumor. Once PNET is diagnosed, multimodal treatment (radical surgery, multidrug chemotherapy, radiotherapy) must be initiated. Despite this, the prognosis is poor if distant metastases are present. Furthermore, palpable tumor masses and synaptophysin expression are associated with a shorter cancer-specific survival.

Adult↗

PubMed2006

Small intestine submucosa in urethral stricture repair in a consecutive series.

OBJECTIVES: To define the feasibility of acellular porcine small intestine submucosa (SIS) as a xenograft implant. SIS is commercially available and approved for use in humans. METHODS: Five patients underwent open surgery for urethral stricture repair using SIS and a four-layer SIS graft. Two patients had a bulbar stricture and three had a combined penile-bulbar stricture. The median stricture length was 9 cm (range 3.5 to 10). All patients underwent at least one internal urethrotomy. The urethral stricture repair was performed as an onlay urethroplasty. SIS was used to augment the urethral caliber at the stricture site. A catheter and percutaneous cystostomy for drainage were placed. The catheter was removed 10 days after surgery. Three weeks postoperatively, voiding cystourethrography and retrograde urethrography were performed. RESULTS: Preoperatively, flow studies were available for 3 patients, in 1 patient voiding was not possible because of urinary retention, and in 1 patient the preoperative flow study was not available (surgery was performed on the basis of the preoperative urethrographic findings). The mean maximal flow rate was 4.2 mL/s (n = 3); the mean value of the mean flow rate was 2.6 mL/s (n = 3). Postoperatively, 1 patient had extravasation, which was treated by prolonged suprapubic drainage. One patient had severe urethritis and one urinary tract infection. Four patients had a recurrent stricture after a mean of 12.4 months (range 3.7 to 17.5). Two patients underwent open repair using buccal mucosa and two refused repeated surgery. CONCLUSIONS: In 4 patients, the operation was not successful. Because of the poor results, we discontinued the use of SIS for open urethral stricture repair.

Aged↗

PubMed2006

Emergent reaction-diffusion phenomena in capillary tubes.

Pattern formation in the Belousov-Zhabotinsky reaction experiments carried out by filling capillary glass tubes with catalyst-immobilized gel for the reaction is reported. Under unperturbed and oscillatory conditions, helicoidal waves appear spontaneously. Quantitative structural data of those helices are obtained by devising an optical tomography technique for extracting rotationally symmetric structures from time-lapse data. Space-time representation of the catalyst oxidation reveals wave transmission phenomenon that is studied further by numerical simulations of a reduced spatial model.

Animals↗

PubMed2005

Origin of bursting oscillations in an enzyme model reaction system.

The transition from simple periodic to bursting behavior in a three-dimensional model system of the hemin-hydrogen-peroxide-sulfite pH oscillator is investigated. A two-parameter continuation in the flow rate and the hemin decay rate is performed to identify the region of complex dynamics. The bursting oscillations emerge subsequent to a cascade of period-doubling bifurcations and the formation of a chaotic attractor in parameter space where they are found to be organized in periodic-chaotic progressions. This suggests that the bursting oscillations are not associated with phase-locked states on a two-torus. The bursting behavior is classified by a bifurcation analysis using the intrinsic slow-fast structure of the dynamics. In particular, we find a slowly varying quasispecies (i.e., a linear combination of two species) which acts as an "internal" or quasistatic bifurcation parameter for the remaining two-dimensional subsystem. A systematic two-parameter continuation in the internal parameter and one of the external bifurcation parameters reveals a transition in the bursting mechanism from sub-Hopf/fold-cycle to fold/sub-Hopf type. In addition, the slow-fast analysis provides an explanation for the origin of quasiperiodic behavior in the hemin system, even though the underlying mechanism might be of more general importance.

Journal Article↗

PubMed2005

Intestinal oxalate absorption in patients with continent urinary diversion.

The objective of the study is to evaluate the post-operative effect of an orthotopic ileal neobladder or a Mainz pouch I bladder replacement on the extent of intestinal oxalate absorption. Gastrointestinal oxalate absorption was measured in six patients with an orthotopic ileal neobladder and in six patients with a Mainz pouch I bladder replacement. The function test applied was the [13C2]oxalate absorption test. With a range of 5.1-12.4%, the oxalate absorption of these patients was well within the reference range for healthy volunteers. The results from our small study indicate that such continent urinary diversions present no hazard for oxalate hyperabsorption and subsequent calcium oxalate urolithiasis.

Aged↗

PubMed2005

Analysis of the oscillatory kinetics of glycolytic intermediates in a yeast extract by FT-IR spectroscopy.

In the present work we demonstrate that FT-IR spectroscopy is a powerful tool for the time resolved and noninvasive measurement of multi-substrate/product interactions in complex metabolic networks as exemplified by the oscillating glycolysis in yeast extract. We found that many of the glycolytic intermediates can be identified with FT-IR spectroscopy. For this, we have constructed a spectral library of most of the glycolytic intermediates and obtained the kinetics of single components in spectra from glycolysing yeast extract by the use of mathematical fitting procedures. The results are in good agreement with the known phase relationships of oscillatory glycolysis. They provide the basis for future application of this method to investigate the energy metabolism of living cells.

Algorithms↗

PubMed2005

Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci.

PURPOSE: Our study was designed to evaluate promoter CpG island hypermethylation in the diagnosis and prognosis of prostate cancer. EXPERIMENTAL DESIGN: Primary prostate cancers from 53 patients, pelvic lymph nodes, noncancerous prostate tissues, and prostate cell lines were analyzed. Real-time methylation-specific PCR was used to identify CpG island hypermethylation at five promising gene loci (i.e., GSTP1, APC, PTGS2, MDR1, and RASSF1a). RESULTS: At three gene loci (GSTP1, APC, and PTGS1) and CpG island, hypermethylation was highly prevalent in prostate cancers (71-91%), and analysis of receiver operator curves showed that hypermethylation at these three gene loci can distinguish between prostate cancer and noncancerous prostatic tissue (i.e., benign hyperplasia) with a sensitivity of 71.1% to 96.2% and a specificity of 92.9% to 100%. Using sensitive SYBR green methylation-specific PCR technology, we observed a respective 28% and 71% hypermethylation rate at the RASSF1a and MDR1 loci in benign prostate hyperplasia, which may represent early nonaggressive carcinogenesis. Methylation characteristics in prostate cancer metastases (i.e., pelvic lymph nodes) were comparable to the respective primary cancer. Statistical analysis showed no correlation between the methylation status of a single gene locus and clinicopathologic variables (e.g., preoperative prostate specific antigen levels, Gleason score, capsular penetration, involvement of seminal vesicle, and age). In contrast, the methylation of two (GSTP1/APC; GSTP1/PTGS2) or three (GSTP1/APC/PTGS2) gene loci correlated with prognostic indicators (i.e., pathologic stage, extraprostatic extension, and Gleason score, but not with prostate specific antigen levels). CONCLUSIONS: Our data suggest that the evaluation of DNA hypermethylation at three gene loci (i.e., GSTP1, APC, and PTGS2) is of diagnostic and prognostic value in prostate cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Glycolytic oscillations and waves in an open spatial reactor: Impact of feedback regulation of phosphofructokinase.

An open spatial reactor has been designed for the investigation of spatio-temporal dynamics of glycolysis. The reactor consists of a diffusive layer made of gel-fixed yeast extract which is in contact with a continuously stirred reservoir to supply this layer with substrates. The coupling between reaction and diffusion in the gel layer enables the formation of spatio-temporal patterns. Temporal oscillations of glycolysis are simply induced by feeding the yeast extract with sugar. Under properly chosen conditions, these oscillations sustain for more than 12 h. A necessary prerequisite for the generation of oscillations is that the ATP concentration in the feeding solution must be high enough to allow for negative feedback of phosphofructokinase. Otherwise, the interplay between ATP-consuming and ATP-producing reactions leads to an unfavorable low ATP/AMP ratio. The generation of travelling NADH-waves is observed in the diffusive layer, when feeding the yeast extract with substrates. Break-up of circular-shaped waves is repeatedly observed, resulting in the formation of rotating NADH-spirals.

Adenosine Monophosphate↗

PubMed2005

Reduction of chemical reaction networks using quasi-integrals.

We present a numerical method to identify possible candidates for quasi-stationary manifolds in complex reaction networks governed by systems of ordinary differential equations. Inspired by singular perturbation theory, we examine the ratios of certain components of the reaction rate vector. Those ratios that rapidly approach a nearly constant value define a slow manifold for the original flow in terms of quasi-integrals, that is, functions that are nearly constant along the trajectories. The dimensionality of the original system is thus effectively reduced without reliance on a priori knowledge of the different time scales in the system. We also demonstrate the relation of our approach to singular perturbation theory which, in its simplest form, is just the well-known quasi-steady-state approximation. In two case studies, we apply our method to oscillatory chemical systems: the 6-dimensional hemin-hydrogen peroxide-sulfite pH oscillator and a 10-dimensional mechanistic model for the peroxidase-oxidase (PO) reaction system. We conjecture that the presented method is especially suited for a straightforward reduction of higher dimensional dynamical systems where analytical methods fail to identify the different time scales associated with the slow invariant manifolds present in the system.

Hemin↗

PubMed2005

Perforating colonic duplication as rare cause of renal abscess in children.

Renal abscess is uncommon in children. In a few cases, ascending infection and/or hematogenous spread have been outlined as pathophysiologic mechanisms in published studies. We report on a 7-month-old female infant who was hospitalized with a high fever. Ultrasonography revealed a hypoechogenic mass in the left kidney. The diagnosis of a renal abscess was confirmed by computed tomography. Because antibiotic treatment had only a transient effect, an open operative procedure was performed. Intraoperatively, a perforating colonic duplication with broad contact to the kidney was found that had destroyed major parts of the kidney's parenchyma. After nephrectomy and complete resection of the colonic duplication, the patient recovered uneventfully.

Abdominal Abscess↗

PubMed2005

New agents in intravesical chemotherapy of superficial bladder cancer.

Although intravesical chemotherapy has been used in the management of superficial bladder cancer for some decades, until recently there has been little or no progress in the search for new agents. However, in the past few years there have been developments of investigational drugs that may play a future role in this indication. This review highlights the mode of action, indications, dose and administration, efficacy, safety and significance of new chemotherapeutic agents such as intravesical valrubicin, gemcitabine, suramin, gamma-linolenic acid, eflornithine (DFMO), tipifarnib (R115777), fenritinide and celecoxib. Although the initial results achieved with these agents in clinical development seem encouraging, long-term data on the prevention of recurrence, disease progression and survival have yet to be obtained.

Administration, Intravesical↗

PubMed2005

Adherens junctions of the human detrusor.

OBJECTIVE: To immunohistochemically identify the protein composition of adherens junctions, which couple smooth muscle cells mechanically, and to confirm their decrease in different bladder dysfunctions, as studies in geriatric bladder dysfunction show fewer such junctions in patients with detrusor overactivity (DO) and bladder outlet obstruction (BOO). MATERIAL AND METHODS: Detrusor biopsies were obtained from video-urodynamically evaluated patients with neurogenic DO (NDO, 31 patients), BOO (six patients) and from six patients with stress urinary incontinence (SUI) with stable, unobstructed detrusors (serving as controls). Specimens were fixed, paraffin-embedded, sectioned, stained with a polyclonal pan-cadherin antibody, monoclonal alpha-, beta- and gamma-catenin antibodies, and a monoclonal integrin-beta1 antibody. All antibodies were known to react with proteins of adherens junctions. Two examiners unaware of sample origin evaluated the sections qualitatively and using a semiquantitative scale. The results were correlated with the patient groups. RESULTS: Specific immunohistochemical staining of pan-cadherin, alpha-, beta- and gamma-catenin could not be detected in any detrusor smooth muscle compartment, but was present in the urothelium. There was integrin-beta1 reactivity in the basement membranes of bladder smooth muscle cells in 38 of 43 detrusor biopsies. There were no differences among the three groups. CONCLUSION: The known proteins of cell-cell adherens junctions are not part of the cell-cell junctions of detrusor smooth muscle. The specific staining of integrin-beta1 indicates either the presence of cell-matrix junctions or of cell-cell junctions within the human detrusor. Further studies are needed to identify the complete protein composition of adherens junctions within smooth muscle cells.

Adherens Junctions↗

PubMed2004

Spiral wave dynamics under feedback control derived from a variety of sensory domains.

The dynamics of rigidly rotating spiral waves in a reaction layer with light-dependent excitability is studied by numerical integration of a reaction-diffusion equation system with a feedback control. The feedback signal is derived from sensory domains with different geometries by introducing an algorithm that computes the illumination intensity to be proportional to the average wave activity in these domains. It is shown that the shape and size of the trajectories of the spiral wave tip as well as the stability of the spiral rotation depend sensitively on the choice of the geometry of the sensory domain. The numerically observed effects are complemented by constructing a flow map based on an analysis of the feedback signal.

Journal Article↗

PubMed2004

Control of glycolytic oscillations by temperature.

External control of oscillatory glycolysis in yeast extract has been performed by application of either homogeneous temperature oscillations or stationary, spatial temperature gradients. Entrainment of the glycolytic oscillations by the 1/2- and 1/3-harmonic, as well as the fundamental input frequency, could be observed. From the phase response curve to a single temperature pulse, a distinct sensitivity of NADH-oxidizing processes, compared with NAD-reducing processes, is visible. Determination of glycolytic intermediates shows that the feedback-regulated phosphofructokinase as well as the glyceraldehyde-3-phosphate dehydrogenase are the most temperature-sensitive steps of glycolysis. We also find strong concentration changes in ATP and AMP at varying temperatures and, accordingly, in the energy charge. Construction of a feedback loop for spatial control of temperature by means of a Peltier element allowed us to apply a temperature gradient to the yeast extract. With this setup it is possible to initiate traveling waves and to control the wave velocity.

Adenosine Diphosphate↗