Biomedical subjects

M Scholz

Publications and source records attributed to M Scholz.

At least 73 records · Page 4Linked to original sources

PubMed2002

Low dose hypersensitivity and induced resistance of V79 cells after charged particle irradiation using 100 MeV/u carbon ions.

This work aimed to study the effects of low dose irradiation in order to detect possible deviations from the linear-quadratic dose dependence of survival after charged particle irradiation. Survival of V79 cells at low doses was studied using a semi-automated cell detection system similar to the DMIPS system. With such a technique, the precision of survival measurements is improved by avoiding the stochastic uncertainties of the conventional dilution assay. A significant hypersensitivity at low doses (0.1 Gy) has been detected for 100 MeV/u carbon ions, whereas for higher doses (up to 0.5 Gy) a transition to a plateau-like region is observed, which is consistent with the assumption of induced resistance. These results are apparently in contrast to earlier studies using high-LET radiation like, e.g. neutrons or negative pions, where the effect of induced resistance has been reported to be at least significantly reduced for single exposure experiments.

Animals↗

PubMed2002

[Osseous processes of the skull--analysis of requirements for robot-assisted surgery].

To design a roboter-assisted trepanation setting of the cranium, an evaluation was done to classify patients with osseous lesions according to pathologies, dimensions and localisations. Emphasis was laid on dimensions and localisation of the pathology to gain information on future configurations of work spaces for robotics in the neurosurgical operation room. All patients with surgery of osseous lesions of the cranium in the years 1993-2001 were evaluated retrospectively. Localisations, dimensions of trepanation and histologic results were evaluated.

Adult↗

PubMed2001

Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin.

Approximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS) are linked to mutations in the SOD1 gene, which encodes the copper/zinc superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from inactivation by reactive oxygen species. We asked whether the protective effect of CuZnSOD on calcineurin is affected by mutations associated with fALS. For this, we monitored calcineurin activity in the presence of mutant and wild-type SOD. We found that the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin-SOD1 interaction in the etiology of fALS.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Human cytomegalovirus circumvents NF-kappa B dependence in retinal pigment epithelial cells.

The human CMV (HCMV) is a persistent virus that may cause severe inflammatory responses especially in immunocompromised hosts. In different cell types, HCMV infection leads to the activation of the pleiotropic transcription factor, NF-kappaB, which triggers virus replication but also propagates cell-mediated inflammatory mechanisms that largely depend on PG synthesis. We investigated the interactions of HCMV and the NF-kappaB-dependent PG synthesis pathway in cultures of retinal pigment epithelial (RPE) cells that are known to be infected in HCMV retinitis patients. Unlike in other cell types, HCMV increased neither NF-kappaB activity nor p65 and p105/50 mRNA levels in RPE cells. Both TNF-alpha and phorbol ester 12,0-tetradecanoylphorbol 13-acetate (TPA) enhanced NF-kappaB activity but only TPA increased HCMV replication. Cyclooxygenase-2 expression and PGE2 release was increased by TPA and TNF-alpha but not by HCMV infection. Stimulatory activity of TPA on HCMV replication was suppressed by protein kinase C inhibitors and inhibitors of p42/44 and p38 mitogen-activated protein kinases but not by NF-kappaB inhibitors. In conclusion, HCMV circumvents the NF-kappaB route in favor of the protein kinase C-dependent mitogen-activated protein kinase pathway in RPE cells. This virus/host cell interaction might be a mechanism that promotes HCMV persistence in immune-privileged organs such as the eye.

Cells, Cultured↗

PubMed2001

Calcineurin regulates slow myosin, but not fast myosin or metabolic enzymes, during fast-to-slow transformation in rabbit skeletal muscle cell culture.

The addition of cyclosporin A (500 ng ml(-1)) - an inhibitor of the Ca2+-calmodulin-regulated serine/threonine phosphatase calcineurin - to primary cultures of rabbit skeletal muscle cells had no influence on the expression of fast myosin heavy chain (MHC) isoforms MHCIIa and MHCIId at the level of protein and mRNA, but reduced the expression of slow MHCI mRNA. In addition, no influence of cyclosporin A on the expression of citrate synthase (CS) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was found. The level of enzyme activity of CS was also not affected. When the Ca2+ ionophore A23187 (4 x 10(-7) M) was added to the medium, a partial fast-to-slow transformation occurred. The level of MHCI mRNA increased, and the level of MHCIId mRNA decreased. Cotreatment with cyclosporin A was able to prevent the upregulation of MHCI at the level of mRNA as well as protein, but did not reverse the decrease in MHCIId expression. The expression of MHCIIa was also not influenced by cyclosporin A. Cyclosporin A was not able to prevent the upregulation of CS mRNA under Ca2+ ionophore treatment and failed to reduce the increased enzyme activity of CS. The expression of GAPDH mRNA was reduced under Ca2+ ionophore treatment and was not altered under cotreatment with cyclosporin A. When the myotubes in the primary muscle culture were electrostimulated at 1 Hz for 15 min periods followed by pauses of 30 min, a partial fast-to-slow transformation was induced. Again, cotreatment with cyclosporin A prevented the upregulation of MHCI at the level of mRNA and protein without affecting MHCIId expression. The nuclear translocation of the calcineurin-regulated transcription factor nuclear factor of activated thymocytes (NFATc1) during treatment with Ca2+ ionophore, and the prevention of the translocation in the presence of cyclosporin A, were demonstrated immunocytochemically in the myotubes of the primary culture. The effects of cyclosporin A demonstrate the involvement of calcineurin-dependent signalling pathways in controlling the expression of MHCI, but not of MHCIIa, MHCIId, CS and GAPDH, during Ca2+ ionophore- and electrostimulation-induced fast-to-slow transformations. The data indicate a differential regulation of MHCI, of MHCII and of metabolism. Calcineurin alone is not sufficient to mediate the complete transformation.

Animals↗

PubMed2001

Application of a fiber-optic NIR-EFA sensor system for in situ monitoring of aromatic hydrocarbons in contaminated groundwater.

Interaction of analyte molecules with the evanescent wave of light guided in optical fibers is among the most promising novel sensing schemes that can be applied for environmental monitoring and on-line process analysis. By combining this measuring principle with the solid-phase extraction of analyte molecules into the polymer cladding of a fiber, it is possible to perform direct absorption measurements in the cladding, if the fiber is adapted to a conventional spectrometer/photometer. A big advantage of this arrangement is that the measurement is scarcely disturbed by matrix effects (background absorption of water in IR measurements, stray light due to turbidity in the sample). By using near-infrared (NIR) evanescent field absorption (EFA) measurements in quartz glass fibers coated with a hydrophobic silicone membrane it is possible to design and construct sensors for monitoring apolar hydrocarbons (HCs) in aqueous matrices.The paper presents a fiber-optic sensor system for the determination of aromatic HCs in groundwater or industrial wastewater. Generally, this instrument is suitable for quantitative in situ monitoring of pollutants such as aromatic solvents, fuels, mineral oils or chlorinated HCs with relatively low water saturation solubility (typically between 0.01 and 10 g l(-1)). The sensor probe is connected via all-silica fibers to a filter photometer developed at the IFIA, thus, allowing even remote analysis in a monitoring well. This portable instrument provides a total concentration signal of the organic compounds extracted into the fiber cladding by measuring the integral absorption at the 1st C--H overtone bands in the NIR spectral range. In situ measurements with the sensor system were performed in a groundwater circulation well at the VEGAS research facility of the University of Stuttgart (Germany). The NIR-EFA sensor system was tested within the frame of an experiment that was carried through in a tank containing sandy gravel with a groundwater-saturated aquifer, where soil and groundwater were contaminated with technical grade xylene. The goal of this experiment was to model and optimize the groundwater circulation well used for the remediation of the aquifer and soil surrounding the well. The sensor proved to trace reliably the total hydrocarbon concentration in the process water pumped from the well to a stripper column. Measurements were performed continuously over 4 months with C8 HC sum concentrations in the process water between 80 mg l(-1) down to the limit of detection, which is around 200 microg l(-1). It could be demonstrated that the fiber-optic sensor system is a valuable tool for near-real-time control of a remedial action technique and verification and documentation of its success.

Environmental Monitoring↗

PubMed2001

Comparison between sheep and human cervical spines: an anatomic, radiographic, bone mineral density, and biomechanical study.

STUDY DESIGN: The quantitative anatomic, radiographic, computerized tomographic, and biomechanical data of sheep and human cervical spines were evaluated. OBJECTIVES: To compare the anatomic, radiographic, computerized tomographic, and biomechanical data of human and sheep cervical spines to determine whether the sheep spine is a suitable model for human spine research. SUMMARY OF BACKGROUND DATA: Sheep spines have been used in several in vivo and in vitro experiments. Quantitative data of the normal sheep cervical spine are lacking, yet these data are crucial to discussion about the results of such animal studies. METHODS: In this study, 20 fresh adult female Merino sheep cervical spines and 20 fresh human cadaver cervical spines were evaluated anatomically, radiographically, computerized tomographically, and biomechanically. Three linear and two angular parameters were evaluated on four digital radiographic views: anteroposterior, right lateral in neutral position, flexion, and extension. Quantitative computed tomography scans at the center of each vertebral body and 3 mm below both endplates were analyzed for bone mineral density measurements. Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending by a nondestructive stiffness method using a nonconstrained testing apparatus. Range of motion and stiffness of each motion segment were calculated. Additionally, 10 linear anatomic parameters of each vertebra were measured using a digital ruler. RESULTS: Anterior and mean disc space height in the sheep cervical spine increased constantly from C2-C3 to C6-C7, whereas middle disc space height decreased and posterior disc space height remained unchanged. Anterior and mean disc space height were significantly higher in sheep. In both sheep and human cervical spines, intervertebral angles were not significantly different. Standard deviations of bone mineral density in the human cervical spine were fourfold higher than in the sheep cervical spine, yet no significant differences were found in bone mineral density values between the two species. Range of motion differed significantly between the two species except in flexion-extension of C3-C4, C5-C6, axial rotation of C2-C3, and lateral bending of C2-C3, C3-C4, and C4-C5. Stiffness also was significantly different except in flexion-extension of C2-C3, C4-C5, C5-C6, and lateral bending of C2-C3, C3-C4, and C4-C5. Anatomic evaluation showed no difference in upper endplate parameters for C4 and C5. CONCLUSIONS: Although several differences were found between human and sheep cervical spines, the small intergroup standard deviations and the good comparability with the human spine encourage the use of the sheep cervical spine as a model for cervical spine research. On the basis of the quantitative data obtained in this study, the sheep motion segment C3-C4 seemed to be the most reliable model for the corresponding human motion segment.

Adult↗

PubMed2001

Visualization of synaptic markers in the optic neuropils of Drosophila using a new constrained deconvolution method.

The fruitfly Drosophila melanogaster offers compelling genetic advantages for the analysis of its nervous system, but cell size precludes immunocytochemical analysis of wild-type structure and mutant phenotypes beyond the level of neuronal arborizations. For many antibodies, especially when immunoelectron microscopy is not feasible, it would therefore be desirable to extend the resolution limit of confocal microscopy as far as possible. Because high-resolution confocal microscopy suffers from considerable blurring, so-called deconvolution algorithms are needed to remove, at least partially, the blur introduced by the microscope and by the specimen itself. Here, we present the establishment and application of a new deconvolution method to visualize synaptic markers in Drosophila optic neuropils at the resolution limit of light. We ascertained all necessary parameters experimentally and verified them by deconvolving injected fluorescent microspheres in immunostained optic lobe tissue. The resulting deconvolution method was used to analyze colocalization between the synaptic vesicle marker neuronal synaptobrevin and synaptic and putative synaptic markers in photoreceptor terminals. We report differential localization of these near the resolution limit of light, which could not be distinguished without deconvolution.

Animals↗

PubMed2001

[Management of craniofacial bone defects with individually prefabricated titanium implants. Follow-up and evaluation of 78 patients with 78 titanium implants 1994-1998].

STUDY: From 1994 to 1998, 78 prefabricated titanium implants were used for the reconstruction of large and complex cranial and craniofacial defects in 76 patients at 19 European centres. After a mean follow-up of 8 months, a clinical and radiological examination was used to determine the results of the reconstruction and the patients' satisfaction. Using a standardized questionnaire patients were also able to comment, subjectively, on improvements or alterations after the insertion of the implant. RESULTS: Two implants were removed after an early infectious complication and in a another two cases the implants were removed in order to obtain a tissue sample for histological examination. All other patients showed constant good to excellent clinical and radiological findings with high patient satisfaction. DISCUSSION: The use of titanium fulfils the highest demands of biocompatibility while at the same time allowing the possibility of an oncological examination using suitable turbo-spinecho-sequences in MRI.

Adolescent↗

PubMed2001

Integrating electrophysiology and neuroimaging of spatial selective attention to simple isolated visual stimuli.

Visual-spatial attention involves modulations of activity in human visual cortex as indexed by electrophysiological and functional neuroimaging measures. Prior studies investigating the time course and functional anatomy of spatial attention mechanisms in visual cortex have used higher-order discrimination tasks with complex stimuli (e.g. symbol matching in bilateral stimulus arrays, or letter discrimination), or simple detection tasks but in the presence of complex distracting information (e.g. luminance detection with superimposed symbols as distractors). Here we tested the hypothesis that short-latency modulations of incoming sensory signals in extrastriate visual cortex reflect an early spatially specific attentional mechanism. We sought evidence of attentional modulations of sensory input processing for simple, isolated stimuli requiring only an elementary discrimination (i.e. size discrimination). As in prior studies using complex symbols, we observed attention-related changes in regional cerebral blood flow in extrastriate visual cortex that were associated with changes in event-related potentials at a specific latency range. These findings support the idea that early in cortical processing, spatially-specific attentional selection mechanisms can modulate incoming sensory signals based on their spatial location and perhaps independently of higher-order stimulus form.

Adult↗

PubMed2001

Inhibition of cytomegalovirus immediate early gene expression: a therapeutic option?

The replication cycle of the human cytomegalovirus (HCMV) is characterized by the expression of immediate early (IE), early (E), and late (L) gene regions. Current antiviral strategies are directed against the viral DNA polymerase expressed during the early phase of infection. The regulation of the IE-1 and IE-2 gene expression is the key to latency and active replication due to their transactivating and repressing functions. There is growing evidence that the pathogenic features of HCMV are largely due to the abilities of IE-1 and IE-2 to transactivate cellular genes. Consequently, current drugs used to inhibit HCMV infection would have no impact on IE-1 and IE-2-induced effects that are produced before the early phase. Moreover, when HCMV DNA replication is inhibited, IE gene products accumulate in infected cells causing disturbances of host cell functions. This review summarizes the biological functions of HCMV-IE gene expression, their relevance in pathogenesis, as well as efforts to develop novel treatment strategies directed against HCMV-IE expression.

Antiviral Agents↗

PubMed2001

The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.

Adult↗

PubMed2001

Vitamin D status, trunk muscle strength, body sway, falls, and fractures among 237 postmenopausal women with osteoporosis.

The aim of this study was to identify factors associated with fractures in patients with postmenopausal osteoporosis. The overall hypothesis was that trunk muscle strength, body sway and hypovitaminosis D would influence daily activities and the likelihood of falls and fractures. - In 237 women (mean age 62.9+/-7.4 years) osteoporosis was defined by a T-score at the femoral neck below -2.5 SD. Trunk muscle strength was determined using isokinetic dynamometry and body sway was measured according to Lord et al. Limitations in everyday life were assessed and the history of falls was documented. A fracture was defined as a vertebral height reduction of more than 20% or at least 4 mm. The assessment was carried out using the Spine Deformity Index (SDI) and was confirmed by an experienced radiologist. Pearson coefficients of correlation were calculated. - After correction for age, significant associations were found for body sway and 25-hydroxyvitamin D (p<0.001), body sway and falls (p<0.001), body sway and rib fractures (p<0.01), trunk muscle strength and limitations in everyday life (p<0.001), trunk muscle strength and SDI (p<0.001), trunk muscle strength and bone density (p<0.001), and bone density and 25-hydroxyvitamin D (p<0.001). No significant correlation was found for trunk muscle strength and 25-hydroxyvitamin D (p=0.712). - Findings suggest that hypovitaminosis D is associated with increased body sway and an elevated risk for falls and falls-related fractures. Musculoskeletal rehabilitation should include strengthening exercises for the trunk muscles and training of neuromuscular co-ordination and balance.

Accidental Falls↗

PubMed2001

Changes of fibrosis-related parameters after high- and low-LET irradiation of fibroblasts.

PURPOSE: To investigate the radiation-induced, premature terminal differentiation and collagen production of fibroblasts after heavy ion irradiation. These endpoints are discussed as an underlying cellular mechanism of fibrosis. MATERIALS AND METHODS: Normal human foreskin fibroblasts (AG1522B) were used to determine clonogenic survival, the premature differentiation and synthesis of extracellular matrix (ECM) proteins, e.g. collagen after irradiation with X-rays, 195 and 11.0 MeV u(-1) carbon ions and 9.9 MeV u(-1) nickel ions. Additionally, biopsies from the skin of minipigs were taken. Similar experiments were carried out after irradiation with X-rays and 195 MeV u(-1) carbon ions. RESULTS AND CONCLUSIONS: RBE for clonogenic survival as well as for fibrosis-related parameters for high-energy carbon ions are slightly above unity. Low-energy carbon ions with a higher LET are more efficient than X-rays, whereas the RBE of nickel ions is below unity. The results obtained for the differentiation pattern and protein production of porcine fibroblasts after irradiation with X-rays and high-energy carbon ions are in agreement with those obtained with human fibroblasts. An accumulation of fibrocytes with a concomitant increase in ECM protein production could be seen after in vitro irradiation. There is no indication of a higher RBE for fibrosis-related parameters compared with other endpoints (survival, chromosomal and DNA damage). The dose- and LET-dependence suggest that premature differentiation is a survival strategy after radiation damage.

Animals↗

PubMed2001

Experimental investigations of the response of films to heavy-ion irradiation.

The response of films to heavy-ion irradiation was investigated systematically by recording dose-response curves for protons and carbon ions in an energy range of 8-430 MeV u(-1). In order to allow for an objective comparison of different experimental results, a practicable method was developed to decouple the value of the net optical density from the film's processing conditions and a precise definition of the film response was deduced. A qualitative explanation of the strong variation of the film response depending on particle type and energy is given, based on the particle's track structure. The data presented here form the basis for using films for dosimetry in mixed particle radiation fields and their application in the heavy-ion therapy project at GSI, Darmstadt.

Carbon↗

PubMed2001

Leukocyte filtration in the early reperfusion phase on cardiopulmonary bypass reduces myocardial injury.

Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I (p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S-GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage.

Aged↗

PubMed2001

Leukocyte filtration in cardiac surgery: a review.

Leukocyte filtration has evolved as an important technique in cardiac surgery with cardiopulmonary bypass to prevent pathogenic effector functions mediated by activated leukocytes. The underlying mechanisms that result in an improvement of laboratory variables as well as clinical outcome are not resolved yet. Moreover, the optimum strategy for the use of current filtration technology has not been systematically evaluated. This paper, therefore, reviews how activated leukocytes may lead to tissue damage, summarizes the known effects of leukocyte filtration on clinical outcome and laboratory parameters, and deals with current experimental and clinical efforts to further limit the pathogenic effects of leukocytes in cardiac surgery.

Adult↗

PubMed2001

Timing of leukocyte filtration during cardiopulmonary bypass.

The effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass (CPB) have been shown by numerous investigators. In the majority of cases a leukocyte filter is placed in the arterial line instead of a standard arterial line filter and used throughout CPB. However, protocols to optimize onset and duration of leukocyte filtration have not been sufficiently evaluated to date. In this paper, current efforts to improve such protocols are demonstrated and discussed. These efforts are based on studies of leukocyte pathogenicity during cardiac surgery. A first study (double-blind randomized) was performed in routine coronary artery bypass graft (CABG) patients to evaluate whether short-term leukocyte filtration during reperfusion by release of the aortic crossclamp would reduce reperfusion-associated myocardial damage. Further data compare the efficacy of three different filtration concepts to reduce CPB- and/or reperfusion-associated leukocyte pathogenicity. Clinical endpoints, standard laboratory variables and functional in vitro assays are provided and discussed.

Cardiopulmonary Bypass↗