Showing papers by "University of Erlangen-Nuremberg published in 2000"

The Vienna classification of gastrointestinal epithelial neoplasia

Abstract: Background—Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large diVerences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. Aim—To develop common worldwide terminology for gastrointestinal epithelial neoplasia. Methods—Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. Results—The large diVerences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/ dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/ dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). Conclusion—The diVerences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status. (Gut 2000;47:251‐255)

Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells

Abstract: The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon γ, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs.

Functional and chemical anatomy of the afferent vagal system.

Abstract: The results of neural tracing studies suggest that vagal afferent fibers in cervical and thoracic branches innervate the esophagus, lower airways, heart, aorta, and possibly the thymus, and via abdominal branches the entire gastrointestinal tract, liver, portal vein, billiary system, pancreas, but not the spleen. In addition, vagal afferents innervate numerous thoracic and abdominal paraganglia associated with the vagus nerves. Specific terminal structures such as flower basket terminals, intraganglionic laminar endings and intramuscular arrays have been identified in the various organs and organ compartments, suggesting functional specializations. Electrophysiological recording studies have identified mechano- and chemo-receptors, as well as temperature- and osmo-sensors. In the rat and several other species, mostly polymodal units, while in the cat more specialized units have been reported. Few details of the peripheral transduction cascades and the transmitters for signal propagation in the CNS are known. Glutamate and its various receptors are likely to play an important role at the level of primary afferent signaling to the solitary nucleus. The vagal afferent system is thus in an excellent position to detect immune-related events in the periphery and generate appropriate autonomic, endocrine, and behavioral responses via central reflex pathways. There is also good evidence for a role of vagal afferents in nociception, as manifested by affective-emotional responses such as increased blood pressure and tachycardia, typically associated with the perception of pain, and mediated via central reflex pathways involving the amygdala and other parts of the limbic system. The massive central projections are likely to be responsible for the antiepileptic properties of afferent vagal stimulation in humans. Furthermore, these functions are in line with a general defensive character ascribed to the vagal afferent, paraventricular system in lower vertebrates.

Analysis of video transmission over lossy channels

Abstract: A theoretical analysis of the overall mean squared error (MSE) in hybrid video coding is presented for the case of error prone transmission. Our model covers the complete transmission system including the rate-distortion performance of the video encoder, forward error correction, interleaving, and the effect of error concealment and interframe error propagation at the video decoder. The channel model used is a 2-state Markov model describing burst errors on the symbol level. Reed-Solomon codes are used for forward error correction. Extensive simulation results using an H.263 video codec are provided for verification. Using the model, the optimal tradeoff between INTRA and INTER coding as well as the optimal channel code rate can be determined for given channel parameters by minimizing the expected MSE at the decoder. The main focus of this paper is to show the accuracy of the derived analytical model and its applicability to the analysis and optimization of an entire video transmission system.

Origin of Surface Conductivity in Diamond

Abstract: Hydrogen-terminated diamond exhibits a high surface conductivity (SC) that is commonly attributed to the direct action of hydrogen-related acceptors. We give experimental evidence that hydrogen is only a necessary requirement for SC; exposure to air is also essential. We propose a mechanism in which a redox reaction in an adsorbed water layer provides the electron sink for the subsurface hole accumulation layer. The model explains the experimental findings including the fact that hydrogenated diamond is unique among all semiconductors in this respect.

Polynomial interpolation in several variables

Abstract: This is a survey of the main results on multivariate polynomial interpolation in the last twenty-five years, a period of time when the subject experienced its most rapid development. The problem is considered from two different points of view: the construction of data points which allow unique interpolation for given interpolation spaces as well as the converse. In addition, one section is devoted to error formulas and another to connections with computer algebra. An extensive list of references is also included.

High dimensional polynomial interpolation on sparse grids

Abstract: We study polynomial interpolation on a d-dimensional cube, where d is large. We suggest to use the least solution at sparse grids with the extrema of the Chebyshev polynomials. The polynomial exactness of this method is almost optimal. Our error bounds show that the method is universal, i.e., almost optimal for many different function spaces. We report on numerical experiments for d = 10 using up to 652 065 interpolation points.

Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds.

Abstract: “Sniffin’ Sticks” is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score – i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject’s age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using “Sniffin’ Sticks.”

The role of nitric oxide in innate immunity.

Abstract: Type 2 nitric oxide synthase (iNOS or NOS2) was originally described as an enzyme that is expressed in activated macrophages, generates nitric oxide (NO) from the amino acid L-arginine, and thereby contributes to the control of replication or killing of intracellular microbial pathogens. Since interferon (IFN)-gamma is the key cytokine for the induction of NOS2 in macrophages and the prototypic product of type 1 T-helper cells, high-level expression of NOS2 has been regarded to be mostly restricted to the adaptive phase of the immune response. In this review, we summarize data that demonstrate a prominent role of NOS2/NO also during innate immunity. During the early phase of infection with the intracellular pathogen Leishmania major, focally expressed NOS2/NO not only exerts antimicrobial activities but also controls the function of natural killer cells and the expression of cytokines such as IFN-gamma or transforming growth factor-beta. Some of these effects result from the function of NOS2/NO as an indispensable co-factor for the activation of Tyk2 kinase and, thus, for interleukin-12 and IFN-alpha/beta signaling in natural killer cells.

Immature dendritic cells generated with low doses of GM‐CSF in the absence of IL‐4 are maturation resistant and prolong allograft survival in vivo

Abstract: Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) (GM(lo) DC) by two different protocols. The phenotype and functional properties of these GM(lo) DC were compared to those of standard BM-DC cultures generated in high concentrations of GM-CSF (GM(hi) DC) or in low GM-CSF plus IL-4 (GM(lo)/IL-4 DC). An effect of IL-4 on maturation was observed only at low but not high doses of GM-CSF. Compared to mature DC, GM(lo) DC were phenotypically immature, weak stimulators of allogeneic and peptide-specific T cell responses, but substantially more potent in presentation of native protein. Immature GM(lo) DC were resistant to maturation by lipopolysaccharide, TNF-alpha or anti-CD40 monoclonal antibodies, as the expression of co-stimulatory molecules was not increased, and stimulatory activity in oxidative mitogenesis was not enhanced. These maturation-resistant immature GM(lo) DC induced T cell unresponsiveness in vitro and in vivo. GM(lo) DC also prolonged haplotype-specific cardiac allograft survival (from 8 days to >100 days median survival time) when they were administered 7 days (but not 3, 14 or 28 days) before transplantation. Our findings may have important implications for future studies in T cell tolerance induction in vivo.

Noninvasive coronary angiography by retrospectively ECG-gated multislice spiral CT.

Abstract: Background—We investigated the applicability and image quality of contrast-enhanced coronary artery visualization by multislice spiral CT using retrospective ECG gating. Methods and Results—Twenty-five patients in sinus rhythm (significant coronary artery stenoses ruled out by invasive angiography) were studied with a multislice spiral CT (Siemens SOMATOM Volume Zoom). In inspiration (mean breathhold, 37 seconds), a volume data set of the heart was acquired (intravenous contrast agent; 4×1-mm slice thickness; 500-ms rotation; table feed, 1.5 mm/360°). Simultaneous recording of the ECG permitted retrospective reconstruction of contiguous cross sections in intervals of 1 mm at any desired interval of the cardiac cycle. The mean duration of the image reconstruction window was 185 ms. Next to 3-dimensional reconstructions of the heart and coronary arteries, multiplanar reconstructions were rendered to determine the visualized length of the coronary arteries, the contrast-to-noise ratio, and the correlation of...

Expression of Advanced Glycation End Products and Their Cellular Receptor RAGE in Diabetic Nephropathy and Nondiabetic Renal Disease

Abstract: Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also identified in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus nephritis. In active lupus nephritis, CML and PENT were detected in the proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes. AGE are also accumulated in acute inflammatory glomerulonephritis secondary to systemic lupus erythematosus, possibly via enzymatic oxidation of glomerular matrix proteins.

Population pharmacokinetics of propofol: a multicenter study.

Abstract: Background:Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.M

Regulation of carbon catabolism in Bacillus species.

Abstract: The gram-positive bacterium Bacillus subtilisis capable of using numerous carbohydrates as single sources of carbon and energy. In this review, we discuss the mechanisms of carbon catabolism and its regulation. Like many other bacteria, B. subtilis uses glucose as the most preferred source of carbon and energy. Expression of genes involved in catabolism of many other substrates depends on their presence (induction) and the absence of carbon sources that can be well metabolized (catabolite repression). Induction is achieved by different mechanisms, with antitermination apparently more common in B. subtilis than in other bacteria. Catabolite repression is regulated in a completely different way than in enteric bacteria. The components mediating carbon catabolite repression in B. subtilis are also found in many other gram-positive bacteria of low GC content.

The benefits of event: driven energy accounting in power-sensitive systems

Abstract: A prerequisite of energy-aware scheduling is precise knowledge of any activity inside the computer system. Embedded hardware monitors (e.g., processor performance counters) have proved to offer valuable information in the field of performance analysis. The same approach can be applied to investigate the energy usage patterns of individual threads. We use information about active hardware units (e.g., integer/floating-point unit, cache/memory interface) gathered by event counters to establish a thread-specific energy accounting. The evaluation shows that the correlation of events and energy values provides the necessary information for energy-aware scheduling policies.Our approach to OS-directed power management adds the energy usage pattern to the runtime context of a thread. Depending on the field of application we present two scenarios that benefit from applying energy usage patterns: Workstations with passive cooling on the one hand and battery-powered mobile systems on the other hand.Energy-aware scheduling evaluates the energy usage of each thread and throttles the system activity so that the scheduling goal is achieved. In workstations we throttle the system if the average energy use exceeds a predefined power-dissipation capacity. This makes a compact, noiseless and affordable system design possible that meets sporadic yet high demands in computing power. Nowadays, more and more mobile systems offer the features of reducible clock speed and dynamic voltage scaling. Energy-aware scheduling can employ these features to yield a longer battery life by slowing down low-priority threads while preserving a certain quality of service.

Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function.

Abstract: Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function

Toward Metal-Capped One-Dimensional Carbon Allotropes: Wirelike C6−C20 Polyynediyl Chains That Span Two Redox-Active (η5-C5Me5)Re(NO)(PPh3) Endgroups

Abstract: Reaction of the butadiynyl complex (η5-C5Me5)Re(NO)(PPh3)(C⋮CC⋮CH) (ReC4H) with Cu(OAc)2 (pyridine, 80 °C) gives the μ-octatetraynediyl complex ReC8Re (70%). Analogous cross-coupling of ReC4H and ReC2H gives (after chromatography) ReC4Re (14%), ReC6Re (44%), and ReC8Re (15%). Longer sp carbon chains are accessed by reactions of ReC4H with n-BuLi and CuI, which give ReC4Cu. This isolable species is treated in situ with BrC⋮CSiEt3 or BrC⋮CC⋮CSiMe3 (excess EtNH2, THF) to give ReC6SiEt3 or ReC8SiMe3 (84−77%). Desilylations (wet n-Bu4N+F-) yield ReC6H or ReC8H (88−73%). Then Cu(OAc)2 (pyridine, 50 °C) gives ReC12Re or ReC16Re (71−67%). The former is also available from ReC4Cu and BrC⋮CC⋮CBr (45%), and ReC10Re can be accessed by cross-coupling. ReC6H and ReC8H are similarly converted to ReC10SiR3 (R = Me, Et; 51−26%) and ReC12SiMe3 (43%). Desilylation of ReC10SiR3 gives labile ReC10H, but only black powder is obtained from ReC12SiMe3. In situ coupling of ReC10H gives ReC20Re (52−34%), which unlike lower homolog...

International recommendations and guidelines for the safe use of diagnostic ultrasound in medicine

Abstract: Modern sophisticated ultrasonographic equipment is capable of delivering substantial levels of acoustic energy into the body when used at maximum outputs. The risk of producing bioeffects has been studied by international expert groups during symposia supported by the World Federation for Ultrasound in Medicine and Biology (WFUMB). These have resulted in the publication of internationally accepted conclusions and recommendations. National ultrasound safety committees have published guidelines as well. These recommendations and safety guidelines offer valuable information to help users apply diagnostic ultrasound in a safe and effective manner. Acoustic output from ultrasound medical devices is directly regulated only in the USA and this is done by the Food and Drug Administration (FDA). However, there is also a modern trend towards self-regulation which has implications for the worldwide use of diagnostic ultrasound. It has resulted in a move away from the relatively simple scheme of FDA-enforced, application-specific limits on acoustic output to a scheme whereby risk of adverse effects of ultrasound exposure is assessed from information provided by the equipment in the form of a real-time display of safety indices. Under this option, the FDA allows a relaxation of some intensity limits, specifically approving the use of medical ultrasound devices that can expose the fetus or embryo to nearly eight times the intensity that was previously allowed. The shift of responsibility for risk assessment from a regulatory authority to the user creates an urgent need for awareness of risk and the development of knowledgeable and responsible attitudes to safety issues. To encourage this approach, it is encumbent on authorities, ultrasound societies and expert groups to provide relevant information on biological effects that might result from ultrasonographic procedures. It is obvious from the continued stream of enquiries received by ultrasound societies that effective dissemination of such knowledge requires sustained strenuous effort on the part of ultrasound safety committees. There is a strong need for continuing education to ensure that appropriate risk/benefit assessments are made by users based on an appropriate knowledge of the probability of biological effects occurring with each type of ultrasound procedure. The primary purpose of this paper is to draw attention to current safety guidelines and show the similarities and areas of general agreement with those issued by the parent ultrasound organisation, the WFUMB. It is equally important to identify gaps in our knowledge, where applicable.

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Abstract: Proinflammatory cytokines contribute to the development of inflammatory and neuropathic pain and hyperalgesia in manyin vivo models. The rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heat-evoked release of calcitonin gene-related peptide from nociceptorsin vitro. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at normal skin temperature of 32°C. However, the cytokines IL-1β, tumor necrosis factor (TNF)-α, and IL-6 but not IL-8 induced a pronounced and transient sensitization of the heat-evoked CGRP release from nociceptors in vitro. This heat sensitization was dose dependent, with EC50 for IL-1β of 2.7 ng/ml and for TNF-α of 3.1 ng/ml. The maximum IL-1β effect reached almost 600% of the heat-evoked release, and the maximum TNF-α effect induced a rise in CGRP release of 350%. In contrast to IL-1β and TNF-α, IL-6 did not induce heat sensitization when applied alone but was only effective in the presence of soluble IL-6 receptor. This suggests a constitutive expression of signaling receptors for TNF and IL-1β and the signal transduction molecule gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine signaling observed in the present study was independent of transcriptional pathways because sensitization occurred on short latency in vitroand under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Our results demonstrate that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy.

Interactive volume on standard PC graphics hardware using multi-textures and multi-stage rasterization

Abstract: Interactive direct volume rendering has yet been restricted to high-end graphics workstations and special-purpose hardware, due to the large amount of trilinear interpolations, that are necessary to obtain high image quality. Implementations that use the 2D-texture capabilities of standard PC hardware, usually render object-aligned slices in order to substitute trilinear by bilinear interpolation. However the resulting images often contain visual artifacts caused by the lack of spatial interpolation. In this paper we propose new rendering techniques that significantly improve both performance and image quality of the 2D-texture based approach. We will show how in ulti-texturing capabilitiesof modern consumer PC graphboards are exploited to enable in teractive high quality volume visualization on low-cost hardware. Furthermore we demonstrate how multi-stage rasterization hardware can be used to efficiently render shaded isosurfaces and to compute diffuse illumination for semi-transparent volume rendering at interactive frame rates.