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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 253 records · Page 14Linked to original sources

Do cells repair precancerous lesions induced by radiation?

The most widely accepted point of view is that cells are endowed with the capacity to repair the primary lesions responsible for cancer induction. In radiobiology, this popular belief evolved from experiments of the same type as those that suggested the existence of sublethal radiation damage repair. The central problem with such data is that the cell-killing component of radiation damage may mask the effects associated with repair of precancerous lesions. The challenge is to separate the two processes that contribute to the observed tumor incidence after irradiation. using a recently developed stochastic model of radiation carcinogenesis allowing for cell death, we provide evidence that precancerous lesions are not subject to repair under certain experimental conditions.

Animals↗

Assessment of posture and motion by multichannel piezoresistive accelerometer recordings.

Modern assessment of posture and motion involves the use of wide bandwidth piezoresistive accelerometers. The direct current (DC) component allows for assessment of slow motion and change in position referring to the gravitational axis: the alternating current (AC) component, calibrated in g. represents acceleration along the sensitive axis of the device. A method study was designed to evaluate the division in DC and AC components, reliabilities, discrimination between conditions, and detection of types of physical activities. Recordings were made in 26 student participants for eight conditions: sitting, standing, lying supine, sitting and typing on a PC keyboard, walking, climbing stairs, walking downstairs, and cycling. This procedure was repeated in reversed order. A classification of physical activities according to the eight conditions (first trial) and based on four parameters, that is DC components trunk, thigh, and lower leg and AC component trunk, was correct in almost 100% of patterns, when applied to the second trial.

Acceleration↗

Cholecystokinin activates CCKB-receptor-mediated Ca-signaling in hippocampal astrocytes.

Cholecystokinin-8S (CCK-8S) is the most abundant neuropeptide in the mammalian cortex and the limbic system; however, its physiological functions remained largely obscure. We studied effects of CCK on astrocytic Ca signaling, which has met considerable interest as a second messenger in astrocytic-neuronal signaling, by digital ratio-imaging of Fura-2/AM loaded rat and mouse hippocampal astrocytes in dissociated culture. Superfusion of CCK-8S (5-50 nM for 2 min) evoked repetitive Ca increases of several hundred nanomolar in a subpopulation of astrocytes. Mouse astrocytes appeared to be more responsive to CCK than rat cells with respect to the fraction of cells responding as well as to the amplitudes of Ca increases. The Ca responses persisted in the absence of extracellular Ca, indicating that release of Ca from intracellular stores is the primary source of these Ca increases. The CCK-8S-induced Ca increases were blocked by the CCKB receptor antagonist PD135158 (100 nM) but not by the CCKA antagonist lorglumide (100 nM). We surmise that astrocytes might be a major primary target for CCK in the CNS.

Animals↗

Rapid increase in inspired desflurane concentration does not elicit a hyperdynamic circulatory response in the pig.

The effects of a rapid increase in inspired desflurane concentration on systemic haemodynamics and plasma catecholamines were studied in seven pigs (22-30 kg). Following premedication (flunitrazepam 0.4 mg/kg i.m.), anaesthesia was induced (propofol 2.5 mg/kg i.v., vecuronium 0.2 mg/kg i.v.), the trachea orally intubated, and ventilation controlled. Anaesthesia was maintained with N2O/O2 (70%/30%), propofol (50 micrograms/kg/min), desflurane (2% end-tidal concentration), and vecuronium (0.3 mg/kg/h). After cannulation of both femoral arteries for subsequent simultaneous systemic pressure measurements and blood sampling for determination of epinephrine (E) and norepinephrine (NE) plasma levels, N2O and propofol were discontinued, and FiO2 and end-tidal concentration of desflurane increased to > 0.9 and 3%, respectively. Forty minutes later, the inspired concentration of desflurane was abruptly increased to 15%. Mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of E and NE were determined before and 1, 2, 4, 8, 16, and 32 min after increasing the desflurane concentration. Plasma concentrations of E and NE were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Data were analysed by repeated measures ANOVA (significance level P < 0.05). The abrupt increase in inspired desflurane concentration caused an insignificant increase (11%) in HR at 1, 2 and 4 min. There was an immediate decrease in MAP. Plasma levels of E and NE remained unchanged throughout. In conclusion, in contrast to findings in humans, a rapid increase in inspired desflurane concentration does not cause a hyperdynamic circulatory response in the pig.

Anesthesia↗

Virtual reality in the operating room of the future.

In cooperation with the Max-Delbrück-Centrum/Robert-Rössle-Klinik (MDC/RRK) in Berlin, the Fraunhofer Institute for Computer Graphics is currently designing and developing a scenario for the operating room of the future. The goal of this project is to integrate new analysis, visualization and interaction tools in order to optimize and refine tumor diagnostics and therapy in combination with laser technology and remote stereoscopic video transfer. Hence, a human 3-D reference model is reconstructed using CT, MR, and anatomical cryosection images from the National Library of Medicine's Visible Human Project. Applying segmentation algorithms and surface-polygonization methods a 3-D representation is obtained. In addition, a "fly-through" the virtual patient is realized using 3-D input devices (data glove, tracking system, 6-DOF mouse). In this way, the surgeon can experience really new perspectives of the human anatomy. Moreover, using a virtual cutting plane any cut of the CT volume can be interactively placed and visualized in realtime. In conclusion, this project delivers visions for the application of effective visualization and VR systems. Commonly known as Virtual Prototyping and applied by the automotive industry long ago, this project shows, that the use of VR techniques can also prototype an operating room. After evaluating design and functionality of the virtual operating room, MDC plans to build real ORs in the near future. The use of VR techniques provides a more natural interface for the surgeon in the OR (e.g., controlling interactions by voice input). Besides preoperative planning future work will focus on supporting the surgeon in performing surgical interventions. An optimal synthesis of real and synthetic data, and the inclusion of visual, aural, and tactile senses in virtual environments can meet these requirements. This Augmented Reality could represent the environment for the surgeons of tomorrow.

Computer Simulation↗

Virtual reality in endonasal surgery.

Virtual environments provide a new dimension of graphic simulation. The interaction between the human and the computer is now intuitive for the user. The use of virtual reality (VR) gives the user the feeling of participating in a (computer generated) scenario very much like reality. This feeling is an essential requirement for simulation of surgical interventions using digital data. Especially in the fields of sinus and skull-base surgery, computer assisted simulation could present a valuable and effective alternative method for honing endoscopic skills. Traditionally, surgeons gain experience through anatomic preparation and education by more experienced colleagues. Landmarks like skull base, carotid arteria or optical nerve have to be identified intraoperatively in order to orientate in this critical region. Highly sensitive structures can be damaged most easily. The quality of surgical skills can be characterized as the sum of knowledge, individual experience and manual dexterity. It is conceivable that a surgeon's level of training and experience could be significantly increased by use of VR. With this in mind, a VR-based simulator for procedures in sinus surgery will improve most of these parts. To provide the virtual environment, a realistic representation of the region of interest with all relevant anatomical structures is required. Based on data from tomographic imaging studies, a three-dimensional representation of the paranasal sinuses is semiautomatically reconstructed. Textures derived from endoscopic images are superimposed on the virtual anatomic structures and provide better realism. Two main components of the VR interface can be distinguished: the 3-D interaction to guide the surgical instruments and the 2-D graphical user interface for visual feedback and control of the session. Moreover, the 3-D interaction has to be realized by means of Virtual Reality techniques providing a simulation of an endoscope and an intuitive handling of other surgical instruments.

Computer Simulation↗

Clostridium perfringens toxins absorbed on filter paper--a simple method for sample conservation.

Clostridium perfringens type C and type D toxins were absorbed on filter paper, dried and stored at room temperature (18-20 degrees C), at 37 degrees C, at 4 degrees C and at -20 degrees C. Type specific toxin was correctly identified in the EIA for 74 days. Absorption on filter paper may offer a simple method for conservation and transport of post mortem samples from cases of suspected enterotoxaemia.

Absorption↗

[Airborne microorganisms in animal stables. 1. Anaerobic airborne bacteria in a calf stable with special regard to Clostridium perfringens].

The total number of airborne anaerobic bacteria with special regard to Clostridium perfringens (C. perfringens) as well as the total number of airborne aerobic bacteria was estimated indoor and outdoor of a calf stable. 65 indoor samples and 63 outdoor samples were collected by using a 6 stage Andersen sampler. The total number of airborne anaerobic bacteria of the indoor samples ranged from 3,216 to 24,222 CFU/m3 (Colony Forming Units) with a part of 4 to 1179 CFU/m3 of C. perfringens. 734 to 1588 CFU/m3 of airborne anaerobic bacteria were found in the outdoor samples. The number of C. perfringens CFU varied between 2 and 15 CFU/m3. The total number of airborne aerobic bacteria indoor ranged from 9,166 to 53,932 CFU/m3, outdoor from 2,443 to 21,205 CFU/m3. Furthermore the results suggested that C. perfringens is suitable for indicating the bacterial contamination of air by faeces of animals.

Air Microbiology↗

On-line hemodiafiltration with pre- and postdilution: a comparison of efficacy.

Since the introduction of on-line substituate preparation, high substituate rates (Qs) in pre- and postdilution for hemodiafiltration (HDF) procedures can be realized. During postdilution HDF (POD-HDF) and additional convective removal is possible, but in vivo Qs is limited to approx. 1/3Qb (bloodflow). With predilution HDF (PRD-HDF) higher Qs and therefore high convective transport rates by ultrafiltration can be reached. On the other hand the blood concentration is diminished by predilution. Further decrease of the diffusive transport is caused by reduced dialysate flow Qd due to separation of the substituate from the dialysate (Fresenius 4008 On-Line HDF, Gambro AK100 Ultra). The theoretical description of the combined diffusive-convective transport is limited to 1-dimensional models and small UF-rates. Therefore for practical and theoretical purposes the assessment of the efficacy of on-line PRD-HDF and POD-HDF in different molecular weight ranges is desirable. By means of in vitro experiments the effective clearances Keff of hemodialysis (HD, dialyzer: Fresenius F60) for urea, creatinine, vitamin B12 and inulin were compared with measured and theoretical Keff of POD- and PRD-HDF. The theoretical expectation is confirmed that Keff for small molecular weight substances decreases slightly with PRD-HDF and increases for larger molecules. In the case of POD-HDF Keff for small molecular weight substances increases slightly and strongly for larger molecules. In vivo experiments were performed to measure the real substance removal from patient's blood and to figure out the impact of dialysate flow (collection of the used dialysate during the 1. treatment hour and concentration measurements for urea, creatinine, phosphate, beta 2-MG). The results show that the subtraction of Qs from Qd reduces Keff for urea, creatinine and phosphate but not for beta 2-MG. PRD-HDF with Qd = 500 ml/min is significantly less effective for small molecules than HD. There is no significant difference of Keff for urea, creatinine, phosphate during HD and PRD-HDF with Qd = 800 ml/min, but a significant increase of 10-15% for POD-HDF. Keff for beta 2-MG increases by 75% for PRD-HDF and 95% for POD-HDF compared with HD (Qd = 500 ml/min).

Adult↗

Cytokine concentration in serum of lupus erythematosus patients: the effect on acute phase response.

In order to get a better insight into cytokine network regulation in systemic lupus erythematosus (SLE), we analyzed levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the sera from 36 SLE patients. Moreover, C-reactive protein (CRP), alpha-1-acid-glycoprotein (AGP), and alpha-1-antichymotripsin (ACT) serum levels were evaluated. Serum levels of IL-10 and IL-6 were significantly increased when compared with healthy controls. TNF-alpha and IFN-gamma did not differ from normal values. We established the relationship between IL-10 and IL-6 as well as between IL-10 and TNF-alpha. None of the analyzed cytokines correlated with the acute phase protein levels. Based on the obtained data, we conclude that IL-10 may play the superior regulating role in SLE. A lack of correlation between the cytokines and acute phase proteins suggests their independence from cytokine regulation.

Acute-Phase Reaction↗

Differentiation of proteinase (minor toxin lambda) in Clostridium perfringens strains from sheep and goats in Iran.

17 Clostridium perfringens strains isolated post mortem from sheep and goats in Iran were examined by biochemical tests and by enzyme immuno assay (EIA). 7 of the C. perfringens strains belonged to type B, 8 strains were type D, one strain was type A, one strain was untypable by EIA. The isolated strains were examined for presence of Minor Toxin Lambda (proteinase) to identify the Iran subtype of C. perfringens type B. The results are compared to characteristics of Clostridium perfringens reference strains. The differentiation technique for proteinase (Minor Toxin Lambda) is discussed.

Animals↗

[Air transportation of day-old chicks with regard to animal welfare].

The transportation of chicks by aircraft increased in the last years greatly. High losses occurred frequently. A very important reason is water and food deprivation for too long a time between hatching and the arrival at the consignee. The process of transportation by aircraft, the development of the animal at hatching, and the clinical and chemical changes caused by water and food deprivation are described. In our opinion pathophysiological conditions are likely to appear 48 hours after hatching, when the animals are not fed and watered. It seems to be necessary to pay more attention to this problem.

Aircraft↗

Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse.

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon.

Animals↗

Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination.

BACKGROUND: The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments. RESULTS: We generated nestin-cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the gamma-chain of the interleukin-2 receptor (IL-2R gamma); in these animals, the IL-2R gamma-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase beta die perinatally, we studied the effects of DNA polymerase beta deficiency in mosaic animals. We found that some of the mosaic polymerase beta-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase beta-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage. CONCLUSIONS: The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase beta, deficient cells are already selected against during embryonic development, demonstrating the general importance of this protein in multiple cell types.

Alleles↗