Showing papers by "University of Duisburg-Essen published in 2002"

Augmentation index is associated with cardiovascular risk

Abstract: Objectives Augmentation index is a parameter measured by pulse wave analysis (PWA) and is used as a surrogate measure of arterial stiffness. The aim of this study was to assess whether augmentation index is associated with cardiovascular risk, as well as to evaluate whether the determinants of augmentation index are different in patients with cardiovascular disease compared to healthy subjects. Design and methods We related augmentation index to risk scores in 216 subjects with or without a cardiovascular disease. Subjects without cardiovascular disease were classified according to the ‘coronary risk chart’ of the European Society of Cardiology (ESC), and those with cardiovascular disease were classified using the SMART (Second Manifestations of ARTerial disease) score and the EPOZ (Epidemiological Prevention study Of Zoetermeer) function. Augmentation index was derived by PWA using carotid applanation tonometry. Augmentation index was also correlated to age, blood pressure, heart rate, smoking history, cholesterol, height, body mass index and gender in subjects categorized as healthy or with cardiovascular disease. Results Augmentation index significantly increased with increasing risk scores (P < 0.0001) and was significantly correlated to cardiovascular risk (ESC: P < 0.0001; SMART: P < 0.0001; EPOZ: P < 0.0001). In subjects with and without cardiovascular disease, augmentation index was correlated with diastolic blood pressure, heart rate, height and gender. Age was found to be significantly correlated with augmentation index only in healthy subjects but not in those with atherosclerotic disease. Conclusions Our findings suggest that augmentation index may be a useful marker of cardiovascular risk. Further studies are required to investigate the relationship between age and augmentation index in subjects with

Mutations of the Selenoprotein N Gene, Which Is Implicated in Rigid Spine Muscular Dystrophy, Cause the Classical Phenotype of Multiminicore Disease: Reassessing the Nosology of Early-Onset Myopathies

Abstract: Multiminicore disease (MmD) is an autosomal recessive congenital myopathy characterized by the presence of multiple, short core lesions (known as "minicores") in most muscle fibers. MmD is a clinically heterogeneous condition, in which four subgroups have been distinguished. Homozygous RYR1 mutations have been recently identified in the moderate form of MmD with hand involvement. The genes responsible for the three other forms (including the most prevalent phenotype, termed the "classical" phenotype) remained, so far, unknown. To further characterize the genetic basis of MmD, we analyzed a series of 62 patients through a combined positional/candidate-gene approach. On the basis of clinical and morphological data, we suspected a relationship between classical MmD and the selenoprotein N gene (SEPN1), which is located on chromosome 1p36 (RSMD1 locus) and is responsible for the congenital muscular dystrophy with rigid spine syndrome (RSMD). A genomewide screening, followed by the analysis of 1p36 microsatellite markers in 27 informative families with MmD, demonstrated linkage to RSMD1 in eight families. All showed an axial myopathy with scoliosis and respiratory failure, consistent with the most severe end of the classical MmD spectrum; spinal rigidity was evident in some, but not all, patients. We excluded linkage to RSMD1 in 19 families with MmD, including 9 with classical MmD. Screening of SEPN1 in the 8 families that showed linkage and in 14 patients with classical sporadic disease disclosed 9 mutations affecting 17 patients (12 families); 6 were novel mutations, and 3 had been described in patients with RSMD. Analysis of three deltoid biopsy specimens from patients with typical RSMD revealed a wide myopathological variability, ranging from a dystrophic to a congenital myopathy pattern. A variable proportion of minicores was found in all the samples. The present study represents the first identification of a gene responsible for classical MmD, demonstrates its genetic heterogeneity, and reassesses the nosological boundaries between MmD and RSMD.

Mutational switch of an IL-6 response to an interferon-γ-like response

Abstract: Signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is central to the responses to the majority of cytokines and some growth factors, including the interferons (IFNs) and the IL-6 family of cytokines. The biological responses to stimulation through the widely distributed IL-6 and IFN-γ receptors are, however, completely different. Remarkably, it is shown here that, in mouse embryo fibroblasts lacking STAT3, IL-6 mediates an IFN-γ-like response including prolonged activation of STAT1, the induction of multiple IFN-γ-inducible genes, the expression of class II MHC antigens, and an antiviral state. Normal cells exposed to IL-6 thus require a STAT3-dependent function(s) to down-regulate STAT1 activity and prevent an IFN-γ-like response. The data encourage the view that the very disparate IFN-γ and IL-6 JAK/receptor complexes mediate a common set of generic or “core” signals which are subject to STAT3-dependent modulation to provide IL-6 specificity. The switching of one cytokine response to one closely mimicking another as a result of the loss of a single signaling component has profound implications, for example, for the interpretation of the phenotypes of knockout mice and for the clinical use of inhibitors of signaling.

Whole-body three-dimensional MR angiography with a rolling table platform: initial clinical experience.

Abstract: A technique for performing whole-body magnetic resonance (MR) angiography with multi-station three-dimensional MR angiography by using a self-developed rolling table platform that integrates the surface coil was evaluated in three volunteers and 10 patients. Use of the surface coil resulted in high signal-to-noise and contrast-to-noise ratios, which translated into sensitivity and specificity of 95.3% and 95.2%, respectively, for detection of significant stenoses (luminal narrowing, >50%) in lower extremity peripheral vascular disease.

Endoscopic treatment of solitary, bilateral, multiple, and recurrent pheochromocytomas and paragangliomas.

Abstract: Because of extensive intraoperative catecholamine release, extreme vascularization, and demanding localization, laparoscopic and retroperitoneoscopic excision of pheochromocytomas and retroperitoneal paragangliomas is challenging. In a prospective clinical study, 61 chromaffin neoplasms (52 pheochromocytomas, 9 paragangliomas) were removed endoscopically from 52 patients (30 males, 22 females; age 44.4 +/- 16.3 years) at 55 operations. Six patients showed multiple (two to five) tumors. Tumor size ranged from 1 to 7 cm (mean 3.6 +/- 1.4 cm). Twelve patients suffered from hereditary diseases. Seven patients had bilateral adrenal diseases; in three patients pheochromocytomas were removed on both sides synchronously. Four neoplasias were local recurrences (three pheochromocytomas, one paraganglioma). The laparoscopic route was chosen for six operations, and the retroperitoneoscopic technique was performed in 49 procedures. Partial adrenalectomy was performed in 19 operations (in all patients with bilateral diseases). High-dosage a-blockage with phenoxybenzamine was routinely used. There were no conversions to open surgery. Perioperative complications were minor (23%), and mortality was zero. The operating time for unilateral pheochromocytomas was 116 +/- 52 minutes (range 35-285 minutes) and depended on tumor size ( or = 3 cm; p <0.01), gender (p <0.01), and extent of resection (partial vs. complete; p <0.05). The operating time for bilateral pheochromocytomas ranged from 285 to 385 minutes, and it was 75 to 600 minutes for paragangliomas. Blood loss was 100 +/- 171 ml. Consumption of analgesics was low (mean 7 mg piritramide postoperatively). The median duration of postoperative hospitalization was 4 days. In six of seven patients with bilateral disease complete preservation of cortical function was achieved. Locoregional metastatic recurrence was found in one patient 3 years after retroperitoneoscopic adrenalectomy. Endoscopic removal of solitary, bilateral, multiple, and recurrent pheochromocytomas and retroperitoneal paragangliomas is feasible and safe but requires extensive experience in minimally invasive and endocrine surgery.

Living-related liver transplantation from the view of the donor: a 1-year follow-up survey.

Abstract: Background. In the past, follow-up surveys for living-related liver transplantation (LRLT) mainly focused on the medical outcome of recipients and donors. In this survey the prevalence of personal, familial, or economic problems of the donors and changes of quality of life after donation were studied. Methods. Questionnaires were sent to 24 donors after right hepatectomy for LRLT (response 92%). The modified EUROTOLD (European Multicenter Study of Transplantation Using Living Donors) questionnaire was used to inquire about the decision-making process, family problems, and economic problems related to the donation. Global quality of life was measured with the SF-36 Health Survey. Results. For most donors the decision to donate was easy or not very difficult (21/22) and was made spontaneously (17/22). The amount of information about the risks of LRLT was limited at the time of decision but increased remarkably immediately before the operation. In 28%, family conflicts occurred (5/22). Retrospectively, all but two donors (91%) would donate again. On average, donors started working after 9 (±3.7) weeks and felt fully recovered after 13 (±7.3) weeks. Adverse financial affects were experienced by 41% of the donors (9/22) because of the donation, and four of those received a compensation. Importantly, quality of life did not differ between donors and nondonors. Conclusion. Donors viewed LRLT positively. Quality of life after donation did not change. However, donors had a prolonged period of physical rehabilitation, and 41% experienced financial disadvantages.

Effects of Selective α1- and α2-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting

Abstract: Background— Coronary flow reserve (CFR) is not normalized shortly after coronary stenting. We hypothesized that α-adrenergic coronary vasoconstriction acts to limit CFR. Methods and Results— We assessed flow velocity by Doppler wires and cross-sectional area by angiography in 46 patients undergoing coronary culprit lesion stenting (81±4% stenosis). Hyperemia was induced by adenosine (24 μg IC or 140 μg/kg per minute IV) before and after stenting. Finally, either the α1-antagonist urapidil (10 mg IC) or the α2-antagonist yohimbine (3 mg IC) was randomly combined with adenosine. In 8 subjects with angiographically normal coronary arteries, CFR was increased from 3.21±0.30 to 3.74±0.43 by yohimbine and to 4.58±0.65 by urapidil, respectively (P=0.0001). Patients were divided according to the cutoff of CFR ≥3.0 (n=18) or <2.5 (n=28). Revascularization per se did not change CFR. However, 15 minutes after stenting, CFR decreased to 2.05±0.55 from CFR 3.64±0.58, whereas in patients with CFR 2.39±0.51, it remained...

Prognostic implication of cardiac troponin T increase following stent implantation

Abstract: Objective: To identify the incidence and clinical significance of myocardial injury following elective stent implantation. Design: Prospective clinical study with 278 consecutive patients undergoing stenting of de novo coronary or saphenous vein graft lesions. Incidence of periprocedural myocardial injury was assessed by analysis of 12 lead ECG, creatine kinase (CK; upper limit of normal (ULN) 70 IU/l for women, 80 IU/l for men), and cardiac troponin T (cTnT; point of care test; threshold 0.1 ng/ml) before and 6, 12, and 24 hours after the intervention. Major adverse cardiac events (MACE: acute myocardial infarction, bypass surgery, and cardiac death) were recorded during clinical follow up (mean (SD) 7.8 (5.3) months). Results: Following elective stenting, the rate of a positive cTnT status was 17.3%, the rate of CK increase of 1–3× ULN 14.7%, the rate of CK increase of > 3× ULN 1.4%, and the rate of Q wave myocardial infarction 0.4%. Cardiac mortality during follow up was higher in patients with postprocedurally increased CK (7.1% v 1.3%, p = 0.01, log rank) and cTnT (9.1% v 0.9%, p v 4.0%, p Conclusions: Following elective stent implantation, a positive cTnT status identified patients at risk of a worse long term outcome. Treatment strategies have to be developed that lead to prognostic improvement by reducing periprocedural myocardial injury.

Oxidative stress decreases G protein-coupled receptor kinase 2 in lymphocytes via a calpain-dependent mechanism

Abstract: G protein-coupled receptor kinase (GRK) 2 plays a crucial role in regulating the extent of desensitization and resensitization of G protein-coupled receptors (GPCRs). We have shown that the expression level of GRK2 in lymphocytes decreases during inflammatory diseases such as arthritis. Reactive oxygen species play an important role in a variety of inflammatory conditions, including arthritis. We demonstrate herein that oxidative stress, induced by exposure of lymphocytes to H(2)O(2), results in a 50% reduction in GRK2 protein levels and GRK activity with no changes in mRNA expression. Treatment of lymphocytes with the tyrosine kinase inhibitor genistein partially reverses the effect of H(2)O(2) on GRK2 levels, although we did not detect direct tyrosine phosphorylation of GRK2. Inhibition of the nonproteasomal protease calpain by calpeptin can prevent the H(2)O(2)-induced GRK2 decrease. In vitro experiments confirm that GRK2 is partially digested by m-calpain in a calcium-dependent way. Functionally, H(2)O(2)-induced decrease in GRK2 levels is associated with an ~70% decrease in agonist-induced beta(2)-adrenergic receptor sequestration. We describe oxidative stress as a novel mechanism for regulation of the intracellular level of GRK2 during inflammatory processes. Moreover, our data demonstrate that oxidative stress may change the functioning of GPCRs via calpain-dependent regulation of GRK2 levels.

Designing Aspect-Oriented Crosscutting in UML

Abstract: The Aspect-Oriented Design Model (AODM) is a new design model for the development of AspectJ programs with the UML. It extends existing UML concepts using standard UML extension mechanisms to provide aspect-oriented concepts as they are found in AspectJ. Further, the AODM specifies how an aspect-oriented design model may be transformed into an ordinary UML design model. It demonstrates how this weaving mechanism may be represented with help of existing UML concepts. The AODM facilitates the perception of aspect-oriented crosscutting in AspectJ programs and carries over the advantages of aspectorientation to the design level. This paper explains the reasoning behind the AODM and demonstrates how it may be used to design aspect-oriented crosscutting in general.

Monetary policy in the Euro area: Lessons from the first years

Abstract: This paper investigates in a consistent semi-structural empirical framework three current issues of monetary policy in the euro area. First, regarding policy transmission we offer a three-stage procedure to combine the efficient estimation of economic structure prior to EMU with current ECB monetary policy. Second, we test whether the regime change leads – before or after – EMU to structural instability. Third, we investigate the stance of monetary policy in Europe. We compare a “counterfactual” ECB reaction function based on average interest rates prior to EMU with actual ECB policy. Furthermore, we compare actual ECB policy with interest rate projections using Bundesbank reaction functions and euroland data.

Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens.

Abstract: Phytohormones and chemical compounds revealing estrogenic effects are of increasing interest for their possible influence on the physiology of the reproductive tract. The gap junction connexin (Cx) genes Cx26 and Cx43, the plasma glycoprotein clusterin gene and the complement C3 gene are highly regulated by estrogen in rat endometrium. To test the value of these genes as markers for estrogenic responsiveness we analyzed the effects of estradiol, diethylstilbestrol, the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen, the phytoestrogens genistein and daidzein, and the industrial compounds DDT (1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl) ethane) and polychlorinated biphenyl (PCB) on the transcription of these genes in rat endometrium in vivo. Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0.03 micro g/250 g body weight (BW), and induction of C3 expression was observed at 0.05 micro g/250 g BW. A comparable effect was obtained by a tenfold higher concentration of diethylstilbestrol. Tamoxifen had a regulatory effect on this set of genes at about a 300-fold higher concentration, while raloxifen revealed much weaker estrogenic activity. No effect on Cx43 transcripts was observed with any of the compounds at the concentrations used. An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts. These results show that Cx26, C3 and clusterin reveal a comparable sensitivity to estrogens and SERMs. With respect to the phytoestrogen genistein, however, Cx26 seems to be the most sensitive gene. The analysis of clusters of estrogen-sensitive endometrial genes could help to identify estrogenic substances, assess their potency, and elucidate their mechanism of action.

Adhesiveness of human uterine epithelial RL95-2 cells to trophoblast: rho protein regulation.

Abstract: Embryo implantation involves adhesion of trophoblast cells to the epithelial lining of the endometrium. Using an in-vitro model to simulate this initial interaction, we previously reported that attachment of human trophoblast-like JAR spheroids to human uterine epithelial RL95-2 cells provokes a Ca 2 influx in RL95-2 cells depending on apically localized integrin receptors. Here, we demonstrate that adhesiveness of RL95-2 cells for JAR spheroids, measured by a centrifugal force-based adhesion assay, is dependent on Rho GTPases, most likely RhoA. Cellular expression and distribution of RhoA were studied by fluorescence confocal microscopy, focusing on the localization of RhoA and F-actin within the adhesion sites between JAR and RL95-2 cells. Contact areas contained high amounts of RhoA and F-actin fibres near the plasma membrane. To determine whether Rho GTPases may influence JAR cell binding, we treated RL95-2 cells with Clostridium difficile toxin A, which specifically inactivates Rho GTPases. Toxin A treatment changed the subcellular distribution of endogenous RhoA in RL95-2 cells and altered RhoA and F-actin colocalization. Adhesion of JAR spheroids to RL95-2 cells treated with toxin A was largely suppressed. These data indicate that Rho GTPases, most likely RhoA, play an important role in uterine epithelial RL95-2 cells for trophoblast binding, and suggest that RhoA may be involved in local signalling cascades during early embryo implantation in vivo.

Quo vadis Mediendidaktik? Zur theoretischen Fundierung von Mediendidaktik

Abstract: Die mediendidaktische Forschung ist gepragt durch Einzelprojekte, in denen die Moglichkeiten neuer Lernmedien erprobt werden. Zur theoretischen Begrundung und Einordnung der Vorhaben werden in der Regel die lerntheoretischen Ansatze des Behaviorismus, Kognitivismus und Konstruktivismus herangezogen. Im vorliegenden Beitrag sollen einige Probleme einer solchen Fundierung von Mediendidaktik diskutiert werden. Die bisherige Theoriebildung in der Mediendidaktik ist durch die Suche nach dem «einen» besten Ansatz des Lernens und Lehrens gepragt. Perspektivisch waren jedoch lerntheoretische und bildungstheoretische Ansatzen starker zu verknupfen. Dabei kann der Pragmatismus sensu Dewey als richtungsweisende Grundlage zur theoretischen Fundierung von Mediendidaktik dienen.

"For whom the bell tolls!" -- innate defense mechanisms and survival strategies of the intestinal epithelium against lumenal pathogens.

Abstract: The intestinal epithelium serves as an essential defensive barrier of the mucosal immune system that forms a bipolar interface between the diverse populations of microbes of the lumen and subjacent immune cells present in the lamina propria. Intestinal epithelial cells express various pattern recognition receptors -- poised to recognize microbial "pathogen-associated molecular patterns" as "non-self" and to rapidly initiate innate immune responses of survival and active defense strategies against lumenal pathogens. Current understanding of the variety of innate immune features present in intestinal epithelium to maintain homeostasis is summarized and the mechanisms through which dysregulation may play a central role in initiation and perpetuation of inflammatory bowel disease are discussed.

Nanostructured Surfaces by Deposition of Metal Nanoparticles by Means of Spray Techniques

Abstract: An electrospray unit was built in order to deposit preformed metal nanoparticles on various substrates. Furthermore, due to treatment of the deposited particles with an oxygen plasma, the particles were stripped of their ligands and strongly fixed to the surface. These treated surfaces can be expected to exhibit properties that differ characteristically from bare surfaces. Depending on the substrate itself, but even more on the size and the density of the deposited nanoparticles, the contact angles and thereby the wettability could be varied drastically. Gold nanoparticles of 17 nm diameter on titanium decreased the contact angle from 82° to 34°, whereas 6–8 nm palladium particles increased the wettabilty to such a degree that a contact angle could not be determined. In contrast to the electrospray technique, a pneumatically operated device was constructed, allowing simultaneous spraying and plasma pyrolysis.

Long-term results of lung volume reduction surgery

Abstract: Objective: Lung volume reduction surgery (LVRS) is effective in the short and intermediate term for the improvement of pulmonary function and subjective symptoms in selected patients with advanced emphysema. The purpose of this study was to examine the long-term functional results of LVRS and to investigate which subgroups would benefit in terms of long-term survival. Methods: All records of the patients who underwent LVRS between 1994 and, 1998 at our hospital were reviewed. Results: Eighty-eight consecutive patients underwent LVRS during the period. There were 62 men and 26 women with an average age of 56.1 years (range 34-72 years). Eleven patients with α1-antitrypsin deficiency were included. The perioperative mortality rate (<90 days) was 2.3% (n = 2). Total lung capacity (7.5 ± 0.3 1) and residual volume (4.8 ± 0.3 1) at 3 years remained lower than baseline (9.2 ± 0.2 1, 6.5 ± 0.2 1, each) (P < 0.001). The mean forced expiratory volume in 1 s (FEV 1 ) at 3 years (0.86 ± 0.081) was higher than baseline (0.78 ± 0.02 1), but the difference did not reach statistical significance. The FEV 1 of the patients with α1-antitrypsin deficiency and of those with respiratory bronchiolitis returned to baseline at one year after LVRS and showed further deterioration. Overall survival rate at 5 years was 71.0% with the mean length of follow-up of 54.2 months. The survival difference was statistically significant between patients with preoperative FEV 1 ≥ 28.5% and those with FEV 1 < 28.5% (P = 0.0152). Conclusions: The improvement of total lung capacity and residual volume persisted long after the operation. Patients with α1-antitrypsin deficiency and those with bronchiolitis showed early deterioration of the lung function. Patients with higher preoperative FEV 1 had a survival benefit. The favorable long-term survival might justify LVRS for the treatment of selected patients with severe emphysema.

Adrenaline‐induced immunological changes are altered in patients with rheumatoid arthritis

Abstract: Objective. To investigate whether in rheumatoid arthritis (RA) patients the immunological changes induced by adrenaline are different from healthy controls (HC). Methods. Fifteen female RA patients and 14 HC were infused with 1 mug/kg adrenaline over 20 min. Blood was drawn before, immediately after, and 1 h after the end of infusion. Lymphocyte subpopulations, cytokine production and natural killer cell cytotoxicity were determined. Results. Subjects exhibited mild cardiovascular changes with no differences between patients and controls. CD16(+)CD56(+)CD3(-) NK cells increased by a factor of 5.7, CD3(+) T cells by 1.5, monocytes by 1.6 and PMN by 1.2 in both groups. The numbers of IL-8- and IL-10-producing monocytes were higher in patients and presented a larger increase after infusion. NK cytotoxic activity was higher in RA patients and increased after infusion in both groups. Activated monocytes and T cells were preferentially recruited in patients and controls. Values returned to baseline 1 h later. Conclusion. We describe an altered response to adrenaline in patients with RA with both pro- and anti-inflammatory effects. Additionally, activated T cells and monocytes recruited to the peripheral blood may influence disease activity.

Chern Classes of Gauss-Manin Bundles of Weight 1 Vanish

Abstract: We show that the Chern character of a variation of polarized Hodge structures of weight one with nilpotent residues at ∞ dies up to torsion in the Chow ring, except in codimension 0. Mathematics Subject Classifications (2000): 14K10, 14C15, 14C40.

Virtual 16 Bit Precise Operations on RGBA8 Textures

Abstract: There is a growing demand for high precision texture formats fed by the increasing number of textures per pixel and multi-pass algorithms in dynamic texturing and visualization. Therefore support for wider data formats in graphics hardware is evolving. The existing functionality of current graphics cards, however, can already be used to provide higher precision textures. This paper shows how to emulate a 16 bit precise signed format by use of RGBA8 textures and existing shader and register operations. Thereby a 16 bit number is stored in two unsigned 8 bit color channels. The focus lies on a 16 bit signed number format which generalizes existing 8 bit formats allowing lossless format expansions, and which has an exact representation of 1, 0 and allowing stable long-lasting dynamic texture updates. Implementations of basic arithmetic operations and dependent texture loop-ups in this format are presented and example algorithms dealing with 16 bit precise dynamic updates of displacement maps, normal textures and filters demonstrate some of the resulting application areas.

Quantum Computing Using Quadrupolar Spins in Solid State NMR

Abstract: Nuclear magnetic resonance (NMR) is a successful method for experimental implementation of quantum information processing. Most of the successful NMR quantum processors are small molecules in liquid state. In this case each spin half particle represents a qubit. Another approach is the usage of higher spin particles as multi qubit systems. We present the first solid state virtual 2-Qubit system, represented by the spin-3/2 nucleus 23Na in a NaNO3 single crystal. For this system we show how to create the pseudo pure states and we derive a set of propagators and logic gates corresponding to the selective excitation of single quantum transitions. With this set, the preparation of an “entangled” state is experimentally verified by state tomography, adjusted to the spin-3/2 system. PACS: 0.367Lx; 76.60-k