PubMed Health⌕ Search

Biomedical subjects

D Wolf

Publications and source records attributed to D Wolf.

At least 19 recordsLinked to original sources
PubMed2006

Automatic lateralization of temporal lobe epilepsy based on scalp EEG.

OBJECTIVE: The objective of this work is the determination of the lateralization of the epileptic seizure onset zone using the scalp EEG signal processing. METHODS: A comprehensive method based on the evaluation of the evolution of the correlation coefficients computed between bipolar channels (longitudinal montage) was applied to 43 patients (87 seizures). The correlation coefficients are estimated by a nonlinear regression analysis. The methodology that leads to the lateralization is based on several processing steps: segmentation, seizure onset determination and then lateralization. RESULTS: Results show that the mean level of the nonlinear correlation values computed between EEG channels at the seizure onset time is significantly higher on the side of the beginning of a seizure. CONCLUSIONS: The side of the seizure onset was determined for about 80-90% of the seizures studied with a satisfactory high reproducibility level. SIGNIFICANCE: Comparison of nonlinear correlation coefficients between both sides of the brain leads to the determination of the side of seizure onset.

Adolescent↗
PubMed2006

Esophageal cancer: determination of internal target volume for conformal radiotherapy.

BACKGROUND AND PURPOSE: To evaluate esophageal tumor and OAR movement during the respiratory cycle in order to obtain optimal values for ITV and PRV. To correlate tumor motion with chest wall displacement - information of value in the free-breathing gating system. MATERIAL AND METHOD: Inclusion criteria were: histologically proven squamous-cell carcinoma (SCC) or adenocarcinoma at stage T3 - T4 NX or TX N1 M0 according to the UICC 1997 classification. Two spiral scans were performed with breath-hold respiration under spirometric control: one at end expiration (EBH) and the other at end inspiration (IBH). Displacements between exhalation and inhalation were calculated according to ICRU report 42 recommendations. For the correlation study, CT-scan acquisition was performed at the isocenter over a 20 - 40 s period. After Fourier Transform, frequency spectra for amplitude and phase of tumor and chest wall motions were performed for each patient. RESULTS: Cumulative distribution of CTV motion in absolute values showed that 95% of data ranged from 0 to 1 cm. Cumulative distribution of GTV motion in absolute values showed that 95% of data ranged from 0 to 0.8 cm. The correlation study demonstrated no specific relationship between respiratory and esophageal motions. CONCLUSION: The ITV margin for 3D conformal radiotherapy in esophageal cancer was 1 cm when 95% of motions were taken into account in this clinical study involving eight patients. Before using a free-breathing gating system, the correlation between external markers and target displacement during irradiation must be established for each patient.

Adenocarcinoma↗
PubMed2005

Detection of specific antibodies to Neospora caninum and Toxoplasma gondii in naturally infected alpacas (Lama pacos), llamas (Lama glama) and vicunas (Lama vicugna) from Peru and Germany.

Sera of an experimentally Neospora caninum infected llama and a non-infected control llama were used to establish an immunoblot, an ELISA and an IFAT to detect antibodies against N. caninum tachyzoites. Subsequently, serum samples collected from a total of 871 South American Camelids (SAC: Lama glama, Lama pacos, Lama vicugna) of two farms in Peru and from 32 SAC of a farm in central Germany were examined for antibodies against N. caninum and Toxoplasma gondii. Based on the recognition of specific bands in the immunoblot, sera of SAC from Peru were differentiated into N. caninum-positive (n = 18) and T. gondii-positive (n = 30) samples and into samples negative or inconclusive for both parasites. Using the immunoblot results as the reference, a modified version of the p38-ELISA and the IFAT were evaluated for detecting N. caninum antibodies in SAC sera. Applying a cut-off as determined by two graph-receiver operating characteristic analysis both, the ELISA and the IFAT, exhibited a sensitivity and specificity of about 95% in the SAC sera from Peru. Serological testing confirmed that SAC may become infected with N. caninum under field conditions in Peru. In addition to alpacas and llamas also 114 wild living vicunas had been examined for antibodies against N. caninum. However, only the alpacas and llamas but no vicunas were found N. caninum-positive. In contrast, T. gondii-seropositive animals were detected in all three SAC species. The lack of N. caninum-seropositive vicunas indicates that in the study area in Peru wild canids might not serve as definitive hosts of N. caninum while for T. gondii a life cycle including wild felids is likely. On the German farm no N. caninum- but only T. gondii-seropositive SAC (n = 14) were detected. The seroprevalence of T. gondii infection was significantly higher in adult SAC (alpacas in Peru, llamas in Germany) than in crias (i.e. < 12 months old foals) indicating that the predominant route of infection is post natal. Since the present study was restricted to a few farms, the seroprevalences determined are not representative. However, our results confirm natural infections with N. caninum and T. gondii in SAC. Whether these infections are linked to any disease, e.g. reproductive losses, has to be clarified in further studies.

Animals↗
PubMed2005

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

OBJECTIVE: To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. METHODS AND RESULTS: Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). CONCLUSION: MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

Aged↗
PubMed2005

[Matching of mammary microcalcifications on images from different views].

PURPOSE: In order to increase sensitivity and specificity in the diagnosis of breast cancer, more than one - generally two or three - mammograms of the same breast are obtained. In order to be able to carry out 3D reconstruction of microcalcification clusters on one hand, and efficiently fuse the information they carry on the other hand, one needs to match corresponding regions of microcalcifications from the different views. Unfortunately, this may be difficult at times. To help the situation, we have developed in this paper, a technique to automatically match microcalcifications found on pairs of mammograms from the same breast. MATERIALS AND METHODS: We used the computed morphological characteristics of individual microcalcifications to build a likeness function to match the microcalcifications. The geometrical constraint suitable for the system used was then applied to reduce the possibilities. From the remaining possibilities, the one with the highest likeness was selected as pair of corresponding microcalcifications. RESULTS: This technique was tested on a number of real cases and yielded 77.14% of good matches. CONCLUSION: This technique provides good results and could therefore be used either directly or for 3D-reconstruction of clustered microcalcifications.

Breast Diseases↗
PubMed2004

[Complete remission of an idiopathic hypereosinophilic syndrome while using imatinib].

HISTORY AND ADMISSION FINDINGS: A 47-year-old man with a hypereosinophilic syndrome (HES), which has been known for 20 years, was admitted to our department due to insufficient therapeutic response to hydroxyurea. In general, the patient felt well, but reported increasing neurological problems, such as ataxia, memory deficits and dysarthria. INVESTIGATIONS: Bone marrow assessments corroborated the diagnosis of a HES. However, we were not able to detect the insertional deletion 4q12 with concomitant fusion of the FIP1L1 to the PDGFRA locus. Magnetic resonance imaging (MRI) indicated a granulomatous vasculitis, which was most likely due to the hematologic malignancy. TREATMENT AND COURSE: : Despite negativity for the FIP1L1-PDGFRA fusion gene, therapy was started with the tyrosine kinase inhibitor Imatinib. This led to a rapid normalization of eosinophilic granulocytes in the peripheral blood as well as in the bone marrow. In addition, the neurologic symptoms substantially improved. CONCLUSION: Imatinib provides a potent therapeutic option in FIP1L1-PDGFRA negative patients suffering from HES.

Benzamides↗
PubMed2004

[Tasks and functions of the "Senate Commission for the Evaluation of Healthy Harmless aspects of Food" of the German Research Foundation].

The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) advises authorities and the government on food safety. The risk assessment of foodstuffs, including novel and functional foods, covers the evaluation of food ingredients and additives as well as the evaluation of novel processing methods. In carrying out this task the Commission expresses its opinion primarily on those aspects which are concerned with the safety assessment. In addition, questions relating to the technological need and to nutritional or physiological benefits are also considered. The topics considered may originate from enquiries of the Ministry for Consumer Protection, Nutrition and Agriculture (BMVEL). Other topics may be selected by the Commission on its own initiative, if they are considered to be of particular importance for consumer protection. Within the context of this activity the SKLM also organises symposia and expert discussions, their outcome subsequently being published as resolutions, conclusions or opinions.

Advisory Committees↗
PubMed2004

Combined transplantation of skeletal myoblasts and bone marrow stem cells for myocardial repair in rats.

OBJECTIVES: To prove whether intramyocardial transplantation of combined skeletal myoblasts (SM) and mononuclear bone marrow stem cells is superior to the isolated transplantation of these cell types after myocardial infarction in rats. METHODS: In 67 male Fischer rats myocardial infarction was induced by direct ligature of the LAD. Seven days postinfarction baseline echocardiography and intramyocardial cell transplantation were performed. Via lateral thoracotomy 200 microl containing either 10(7) SMs or 10(7) bone marrow-derived mononuclear cells (BM-MNC) or a combination of 5x10(6) of both cell types (MB) were injected in 10-15 sites in and around the infarct zone. In controls (C) 200 microl of cell-free medium were injected in the same manner. Before injection both cell types were stained using a fluorescent cell linker kit (PKH, Sigma). In addition, SMs were transfected with green fluorescent protein. Nine weeks postinfarction follow-up echocardiography was performed and animals were sacrificed for further analysis. RESULTS: At baseline echocardiography there was no difference in left ventricular ejection fraction (LVEF; C, SM, BM-MNC, MB: 60.1+/-3.2, 53.3+/-10.2, 53.1+/-8.7, 49+/-9.0%) and left ventricular end diastolic diameter (LVEDD; C, SM, BM-MNC, MB: 6.5+/-0.8, 5.17+/-0.8, 5.77+/-1.4, 6.25+/-0.8 mm) between the different therapeutic groups. Eight weeks after cell transplantation LVEDD was significantly increased in all animals except those that received a combination of myoblasts and bone marrow stem cells (MB; C, SM, BM-MNC, MB: 7.7+/-0.6 mm, P=0.001; 7.7+/-1.5 mm, P<0.001; 7.7+/-1.1 mm, P=0.005; 6.6+/-1.7 mm, P=0.397. At the same time LVEF decreased significantly in the control group (C), stayed unchanged in animals that received bone marrow stem cells (BM-MNC) and increased in animals that received myoblasts (SM) and a combination of both cell types (MB; C, SM, BM-MNC, MB: 45.3+/-7.0%, P=0.05; 63.9+/-15.4%, P=0.044; 54.3+/-6.3%, P=0.607; 63.0+/-11.5%, P=0.039). CONCLUSIONS: The present data show that the concept of combining SMs with bone marrow-derived stem cells may be of clinical relevance by merging the beneficial effects of each cell line and potentially reducing the required cell quantity. Further studies are required to identify the exact mechanisms underlying this synergy and to allow full exploitation of its therapeutic potential.

Animals↗
PubMed2003

Deformation-mechanism map for nanocrystalline metals by molecular-dynamics simulation.

Molecular-dynamics simulations have recently been used to elucidate the transition with decreasing grain size from a dislocation-based to a grain-boundary-based deformation mechanism in nanocrystalline f.c.c. metals. This transition in the deformation mechanism results in a maximum yield strength at a grain size (the 'strongest size') that depends strongly on the stacking-fault energy, the elastic properties of the metal, and the magnitude of the applied stress. Here, by exploring the role of the stacking-fault energy in this crossover, we elucidate how the size of the extended dislocations nucleated from the grain boundaries affects the mechanical behaviour. Building on the fundamental physics of deformation as exposed by these simulations, we propose a two-dimensional stress-grain size deformation-mechanism map for the mechanical behaviour of nanocrystalline f.c.c. metals at low temperature. The map captures this transition in both the deformation mechanism and the related mechanical behaviour with decreasing grain size, as well as its dependence on the stacking-fault energy, the elastic properties of the material, and the applied stress level.

Computer Simulation↗
PubMed2003

Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival.

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer.

Adult↗
PubMed2002

Dosage form-related food interaction observed in a marketed once-daily nifedipine formulation after a high-fat American breakfast.

OBJECTIVE: Objective of the study was the comparison of two nifedipine sustained-release products marketed in Europe. Maximum plasma concentration (C(max)) and area under the plasma-concentration curve (AUC) values were derived after administration of single doses (60 mg) of test product and reference product, both approved for once-a-day administration, to 24 healthy male volunteers either after an overnight fast or immediately after a high-fat American breakfast. The study was performed with a randomised, non-blinded, four-period crossover design. Within- and between-product comparisons were determined for fed versus fasted administration considering bioavailability and tolerability of all treatments. Furthermore, in vitro dissolution characteristics of both products were evaluated. METHODS: Plasma samples were assayed using a liquid chromatography-mass spectrometry method, and resulting pharmacokinetic parameters were determined model independently according to international requirements and the current European guidelines. RESULTS: Under fasted conditions the comparison of test and reference products showed a similar extent of bioavailability with a mean ratio of AUC((0-)(infinity)()) of 99% [95% confidence interval (CI) 86%, 114%], but significantly higher C(max) values resulting in a mean ratio of 169% (95% CI 139%, 206%). Accordingly, mean residence time and half-value duration values were smaller for the test product than the reference product. Under fed conditions, a pronounced food effect could be observed for the test product resulting in a pronounced increase of C(max) values. The affiliating point estimate was calculated as 340% with a 95% CI of 279%, 413%. However no remarkable influence of food intake was observed for the reference product. CONCLUSION: Under fasting conditions the modified-release characteristics of the test product are less pronounced than the reference product. No relevant impact of food intake could be observed for the reference product when switching from fasted to fed state, whereas a significant loss of modified-release characteristics could be detected for the test product under fed conditions resulting in much higher maximum concentrations. Such a phenomenon has been described in literature as "dose-dumping effect".

Adult↗
PubMed2002

The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast.

AIMS: The aim of this study was to investigate the effect of concomitant food intake on the bioavailability of two nifedipine containing modified release dosage forms for once daily administration. The clinical study was performed to investigate the in vivo relevance of pH-dependent differences in the in vitro release properties of the two dosage forms. METHODS: This was a randomized, open, 4-way crossover study in 24 healthy, male subjects. Following an overnight fast of 12 h single doses of Adalat OROS or Slofedipine XL were administered either in the fasted state or immediately after a high fat American breakfast. Nifedipine plasma concentrations in samples obtained until 48 h after drug administration were determined using a validated LC-MS/MS method. Calculation of pharmacokinetic parameters was conducted model-independently. The two dosage forms as well as the two administration conditions were compared by calculating point estimates and 90% confidence intervals for the relevant pharmacokinetic parameters. In vitro dissolution tests were performed using a paddle apparatus 3 acc. USP, a pharmacopoeial dissolution system consisting of reciprocating cylinders in flat-bottomed glass vessels, with various buffer systems covering the entire physiological pH-range of the gastrointestinal tract. RESULTS: After fasted administration the extent of bioavailability of nifedipine as characterized by AUC(0,infinity) was slightly lower for Slofedipine XL compared with Adalat OROS with a point estimate of 82.3% primarily resulting from pronounced differences in nifedipine concentrations during the first 15 h after administration. Accordingly, maximum plasma concentrations were lower after administration of Slofedipine XL compared with Adalat OROS (point estimate: 84.3%). Under fed conditions the differences in bioavailability between the two products as characterized by the pharmacokinetic parameters AUC(0,tn) and Cmax were greater than after fasting conditions with point estimates of 69.6% and 81.0%, respectively. However, most striking was a pronounced delay in nifedipine absorption observed under fed conditions after administration of Slofedipine XL which resulted in lag-times of more than 15 h in 15 out of 24 subjects. Owing to this lag-time under fed conditions the relative bioavailability of nifedipine from Slofedipine XL compared with Adalat OROS was only 28% over the intended dosing interval of 24 h. CONCLUSIONS: In this study a dosage form-dependent food interaction was observed which, under fed conditions, resulted in pronounced differences in the relative bioavailability of nifedipine between Slofedipine XL and Adalat OROS over the intended dosing interval of 24 h. The delay in nifedipine absorption when Slofedipine XL is administered after a high-fat breakfast may be explained by the formulation properties. Slofedipine XL is an erosive tablet with an acid resistant coating whereas Adalat OROS is designed with an osmotic push-pull system. Under fed conditions drug from the single unit enteric coated dosage form exhibits a delayed absorption probably due to an extensively prolonged gastric residence time which does not allow drug release, on the other hand the osmotically driven push-pull system is not sensitive to concomitant food intake. The observed phenomenon might be of therapeutic relevance. For example a change from taking Slofedipine XL in the fed to the fasted state might result in increased systemic concentrations of nifedipine.

Administration, Oral↗
PubMed2001

A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells.

In the infected host, the Nef protein of HIV/SIV is required for high viral loads and thus disease progression. Recent evidence indicates that Nef enhances replication in the T cell compartment after the virus is transmitted from dendritic cells (DC). The underlying mechanism, however, is not clear. Here, we report that a natural variability in the proline-rich motif (R71T) profoundly modulated Nef-stimulated viral replication in primary T cells of immature dendritic cell/T cell cocultures. Whereas both Nef variants (R/T-Nef) downregulated CD4, only the isoform supporting viral replication (R-Nef) efficiently interacted with signaling molecules of the T cell receptor (TCR) environment and stimulated cellular activation. Structural analysis suggested that the R to T conversion induces conformational changes, altering the flexibility of the loop containing the PxxP motif and hence its ability to bind cellular partners. Our report suggests that functionally and conformationally distinct Nef isoforms modulate HIV replication on the interaction level with the TCR-signaling environment once the virus enters the T cell compartment.

Amino Acid Motifs↗
PubMed2001

Pure compound libraries; a new perspective for natural product based drug discovery.

What often distinguishes the leaders in drug discovery and development from the rest is the quality of their compound libraries and the ease of access that they have to the information within those libraries. The screening of natural products can provide greater structural diversity than standard synthetic chemistry and offers significant opportunities for finding novel low molecular weight lead compounds. However, which strategy is the best for natural-product-based drug discovery? Two well established but relatively time consuming approaches are the screening of crude extracts and pre-fractionated extracts. This case study describes a third, pure-compound-screening approach, and discusses its benefits and pitfalls.

Journal Article↗
PubMed2001

Differential localization of HDAC4 orchestrates muscle differentiation.

The class II histone deacetylases HDAC4 and HDAC5 interact specifically with the myogenic MEF2 transcription factor and repress its activity. Here we show that HDAC4 is cytoplasmic during myoblast differentiation, but relocates to the nucleus once fusion has occurred. Inappropriate nuclear entry of HDAC4 following overexpression suppresses the myogenic programme as well as MEF2-dependent transcription. Activation of the Ca(2+)/calmodulin signalling pathway via constitutively active CaMKIV prevents nuclear entry of HDAC4 and HDAC4-mediated inhibition of differentiation. Consistent with a role of phosphorylation in HDAC4 cytoplasmic localisation, HDAC4 binds to 14-3-3 proteins in a phosphorylation-dependent manner. Together these data establish a role for HDAC4 in muscle differentiation. Recently, HDAC5 has also been implicated in muscle differentiation. However, despite the functional similarities of HDAC4 and HDAC5, their intracellular localisations are opposed, suggesting a distinct role for these enzymes during muscle differentiation.

14-3-3 Proteins↗
PubMed2001

Protective effect of XY99-5038 on hydrogen peroxide induced cell death in cultured retinal neurons.

XY99-5038 is a preparation from a specific formula provided by Dr. Yan Xin, a renowned Traditional Chinese Medicine specialist. This formulation has proven to be effective without side effects but has not been studied under rigorous laboratory conditions. In order to investigate the role of XY99-5038 in protecting neurons from degeneration, we used retinal neuronal culture as a model system to study the protective effects of XY99-5038 against hydrogen peroxide (H2O2) induced cytotoxicity. Basic fibroblast growth factor (bFGF), a potent neurotrophic factor, was employed as comparable agent. Retinas of 0-2 days old Sprague-Dawley rats were isolated, dissociated, and the neurons maintained for 2 weeks in a synthetic serum-free media. Cytotoxicity was determined by MTT (3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) and LDH (Lactate dehydrogenase) assays, whereas apoptotic cell death was evaluated by the TUNEL (TdT-mediated digoxigenin-dUTP nick-end labeling) assay. Treatment with H2O2 significantly induced death of retinal neurons. Pretreatment with XY99-5038 prior to insult greatly inhibited or attenuated H2O2 induced cytotoxicity and apoptosis. These effects were shown to be dose-dependent. Our data also show that the protective effect of XY99-5038 is more potent than that of bFGF. Our data suggest that XY99-5038 could be a potential agent in the treatment of disorders associated with oxidative damage.

Animals↗