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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 37 records · Page 2Linked to original sources

Three-dimensional imaging of atomic four-body processes.

To understand the physical processes that occur in nature we need to obtain a solid concept about the 'fundamental' forces acting between pairs of elementary particles. It is also necessary to describe the temporal and spatial evolution of many mutually interacting particles under the influence of these forces. This latter step, known as the few-body problem, remains an important unsolved problem in physics. Experiments involving atomic collisions represent a useful testing ground for studying the few-body problem. For the single ionization of a helium atom by charged particle impact, kinematically complete experiments have been performed since 1969 (ref. 7). The theoretical analysis of such experiments was thought to yield a complete picture of the basic features of the collision process, at least for large collision energies. These conclusions are, however, almost exclusively based on studies of restricted electron-emission geometries. Here, we report three-dimensional images of the complete electron emission pattern for the single ionization of helium by the impact of C6+ ions of energy 100 MeV per a.m.u. (a four-body system) and observe features that have not been predicted by any published theoretical model. We propose a higher-order ionization mechanism, involving the interaction between the projectile and the target nucleus, to explain these features.

Journal Article↗

Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics.

In order to assess the significance of drug levels measured in clinical and forensic toxicology as well as for Therapeutic Drug Monitoring (TDM) it is essential that good collections of data are readily available. For more than 800 substances, therapeutic ('normal') and, if data was available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. The compilation includes data for hypnotics, benzodiazepines, neuroleptics, antidepressants, sedatives, analgesics, anti-inflammatory agents (e.g., NSAIDs), antihistamines, antiepileptics, betaadrenergic antagonists, antibiotics (penicillins, cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel blockers, cardiac glycosides, antiarrhythmics, antiasthmatics, ACE-inhibitors, opiate agonists, and local anesthetics, among others. In addition, toxicologically relevant xenobiotics were listed. Data have been abstracted from published information, both compilations and primary sources and have been completed with data collected in our own forensic and clinical toxicology laboratories. Wherever possible, ranges for therapeutic plasma concentrations are expressed as trough concentration at steady state. The half-life values given for each drug are chosen to represent the terminal log-linear phase at most. It is the purpose to rapidly assess the significance of drug levels for the therapeutic monitoring of patients, and to facilitate the diagnostic and clinical assessment in case of intoxications.

Animals↗

Fast Kawasaki spin exchange limit of spin-facilitated kinetic Ising models.

We study a Fock-space operator technique for describing the stochastic kinetics of a spin-facilitated kinetic Ising model. We focus in particular on the diffusion (fast Kawasaki exchange) limit in which the kinetics can be described by a single mean field evolution equation. We derive some general criteria for the approximative validity of mean field theory for the case of a nondiverging diffusion coefficient of the local spin states.

Journal Article↗

Simultaneous projectile-target ionization: a novel approach to (e, 2e) experiments on ions.

A kinematically complete experiment for simultaneous ionization of a projectile and target has been performed for 3.6 MeV/u C2+ on He collisions measuring the final vector momenta of the He1+ recoil ion and of two electrons (projectile, target) in coincidence with the emerging C3+ projectile. The feasibility of an event-by-event separation of the various reaction channels, among them the ionization of C2+ by the interaction with a quasifree target electron, is demonstrated in agreement with six-body classical trajectory Monte Carlo calculations, paving the way to kinematically complete electron-ion scattering experiments.

Journal Article↗

Complete remission of a primary cutaneous B-cell lymphoma of the lower leg by first-line monotherapy with the CD20-antibody rituximab.

BACKGROUND: Rituximab is a genetically engineered antibody recognizing the CD20 antigen known to be expressed by more than 95% of B-cell lymphomas. Recently the antibody has been approved for routine administration in primary extracutaneous, treatment-refractory or relapsed low-grade, follicular non-Hodgkin B-cell lymphomas. With regard to the pathogenetically related primary cutaneous lymphomas, the so-called large B-cell lymphoma of the leg represents a distinct, but rare subentity. In an 89-year-old, multimorbid patient who was affected by such a non-resectable CD20+ large B-cell lymphoma limited to the skin of both lower legs, rituximab was used as a first-line monotherapy in order to avoid local or systemic toxicities inevitably linked to conventional treatment modalities, i.e., radio- or chemotherapy. METHODS: Rituximab was administered at a dosage of 375 mg/m(2) i.v. eight times in weekly intervals. As a premedication we used prednisolone 150 mg i.v. as well as loratadine 10 mg p.o. 1 h before each rituximab infusion. RESULTS: The treatment was well tolerated without any adverse reactions, but was accompanied by a mild transient blood eosinophilia. The histologically proven, exophytic, multi-nodular lymphoma showed a substantial regression already at 2 weeks after the onset of the rituximab treatment. At 8 weeks we observed a complete clinical remission which is now stabile for a follow-up period of 6 months without any maintenance therapy. CONCLUSIONS: Our case observation demonstrates that an intensified, i.e. eightfold, rituximab application in weekly intervals may be a highly effective, tumor target cell-specific first-line monotherapy in the management of primary cutaneous large B-cell lymphoma of the leg. Given the rareness of the disease, the result as well as the possible contribution of the prednisolone premedication will have to be evaluated in a future, controlled, multi-centre study.

Aged↗

Recent weight changes and weight cycling as predictors of subsequent two year weight change in a middle-aged cohort.

OBJECTIVE: To evaluate the influence of recent weight changes (weight gain, loss and cycling) on subsequent weight changes. DESIGN: Prospective cohort study with 2 y of follow-up. Data analysis with a polytomous logistic regression model. SUBJECTS: A total of 18 001 non-smoking subjects, 6689 men and 11 312 women, from the general population. MEASUREMENTS: Body height and weight measurements and interview data on lifestyle habits and medical history at baseline. For follow-up, self-administered questionnaires for assessment of body weight and incident diseases. RESULTS: Recent changes in body weight, that is weight gain, weight loss and weight cycling, were significant predictors of subsequent weight changes in both men and women after controlling for age, baseline BMI and several lifestyle and behavioural characteristics as potential confounding factors. Weight cycling before baseline was the strongest predictor of subsequent large weight gain (> or =2 kg) with an odds ratio (OR) of 4.84 (95% confidence interval (CI) 3.34-7.02) in men. In women, prior weight loss was the strongest predictor of subsequent large weight gain (OR 4.77; 95% CI 3.63-6.03), followed by weight cycling (OR 3.02; 95% CI 2.15-4.25). CONCLUSION: These data indicate the need for thorough weight history assessment to identify those who are most likely to gain weight. Effective weight control before the development of obesity or after intentional weight loss due to obesity should be a primary goal in the management of obesity.

Adolescent↗

Indirect immunofluorescence using monoclonal antibodies for the detection of leukocytospermia: comparison with peroxidase staining.

The presence of increased number of leukocytes in semen is indicative of inflammation in the male genital tract. Inflammatory processes at this level may lead to marked impairment of sperm function, and finally to a reduction in their fertilizing capability. An immunocytological technique for the detection of seminal leukocytes was evaluated in this study. As part of the standardization technique, different fixation methods were tested to ascertain whether samples could be stored and examined later. It was found that fixation with cold acetone at freezing temperatures retained immunoreactivity until day 11 of storage. All other methods showed a significant loss of immunoreactivity, from as little as day 2 of storage. In 46 specimens with elevated numbers of round cells, number of peroxidase-positive cells and number and type of leukocytes were evaluated by means of indirect immunofluorescence. Determination of peroxidase-positive cells to detect leukocytospermia, the standard procedure recommended by the WHO, was compared with the indirect immunofluorescence technique using monoclonal antibodies. While 19 of 46 patients showed high numbers of leukocytes in the ejaculate, as determined by the immunocytological method, only 9 of these were identified to be leukocytospermic, according to the WHO (standard) procedure. This difference was statistically significant (P < 0.01) and indicates that the standard method of detection of seminal leukocytes may be inaccurate.

Acetone↗

Consumption of added fats and oils in the European Prospective Investigation into Cancer and Nutrition (EPIC) centres across 10 European countries as assessed by 24-hour dietary recalls.

OBJECTIVE: To evaluate the consumption of added fats and oils across the European centres and countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN AND SETTING: 24-Hour dietary recalls were collected by means of standardised computer-guided interviews in 27 redefined EPIC centres across 10 European countries. SUBJECTS: From an initial number of 36 900 subjects, single dietary recalls from 22 924 women and 13 031 men in the age range of 35-74 years were included. RESULTS: Mean daily intake of added fats and oils varied between 16.2 g (Varese, Italy) and 41.1 g (Malmö, Sweden) in women and between 24.7 g (Ragusa, Italy) and 66.0 g (Potsdam, Germany) in men. Total mean lipid intake by consumption of added fats and oils, including those used for sauce preparation, ranged between 18.3 (Norway) and 37.2 g day-1 (Greece) in women and 28.4 (Heidelberg, Germany) and 51.2 g day-1 (Greece) in men. The Mediterranean EPIC centres with high olive oil consumption combined with low animal fat intake contrasted with the central and northern European centres where fewer vegetable oils, more animal fats and a high proportion of margarine were consumed. The consumption of added fats and oils of animal origin was highest in the German EPIC centres, followed by the French. The contribution of added fats and oils to total energy intake ranged from 8% in Norway to 22% in Greece. CONCLUSIONS: The results demonstrate a high variation in dietary intake of added fats and oils in EPIC, providing a good opportunity to elucidate the role of dietary fats in cancer aetiology.

Adult↗

Consumption of dairy products in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: data from 35 955 24-hour dietary recalls in 10 European countries.

OBJECTIVES: To describe and compare the consumption of dairy products in cohorts included in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Data from single 24-hour dietary recall interviews collected through a highly standardised computer-based program (EPIC-SOFT) in 27 redefined centres in 10 European countries between 1995 and 2000. From a total random sample of 36 900, 22 924 women and 13 031 men were selected after exclusion of subjects under 35 and over 74 years of age. RESULTS: A high total consumption of dairy products was reported in most of the centres in Spain and in the UK cohort sampled from the general population, as well as in the Dutch, Swedish and Danish centres. A somewhat low consumption was reported in the Greek centre and in some of the Italian centres (Ragusa and Turin). In all centres and for both sexes, milk constituted the dairy sub-group with the largest proportion (in grams) of total dairy consumption, followed by yoghurt and other fermented milk products, and cheese. Still, there was a wide range in the contributions of the different dairy sub-groups between centres. The Spanish and Nordic centres generally reported a high consumption of milk, the Swedish and Dutch centres reported a high consumption of yoghurt and other fermented milk products, whereas the highest consumption of cheese was reported in the French centres. CONCLUSION: The results demonstrate both quantitative and qualitative disparities in dairy product consumption among the EPIC centres. This offers a sound starting point for analyses of associations between dairy intake and chronic diseases such as cancer.

Adult↗

Relaxin enhances in-vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases.

Until recently, relaxin (RLX) has been known predominantly for its effects on the reproductive system, where it induces remodelling of the extracellular matrix and up-regulation of matrix metalloproteases (MMPs). In solid cancers, tissue remodelling and MMP activation are essential for invasion and metastasis. We therefore investigated the effect of RLX on invasiveness and MMP expression of human breast cancer cell lines. Upon incubation with porcine RLX, the invasiveness of SK-BR3 cells was significantly increased. Similar effects could be achieved in MCF-7 cells, especially when RLX was combined with epidermal growth factor. Enhanced invasiveness was accompanied by up-regulation of MMP production and could be almost completely blocked by the MMP inhibitor FN 439. Zymography revealed increased secretion of MMP-2, -7 and -9, associated with up-regulated mRNA concentrations of MMP-2, -9, -13 and -14. mRNA expression levels of MMP-1, -3, -7, -8, -10, -11, -12 and of tissue inhibitors of metalloproteases-1, -2, -3 and -4 were either very low or not detectably influenced by RLX. Taken together, RLX enhances in-vitro invasiveness of breast cancer cell lines by induction of MMP expression. It remains to be clarified whether RLX might play a similar role in vivo and promote tumour progression.

Breast Neoplasms↗

Occupational exposure assessment in case-control studies: opportunities for improvement.

Community based case-control studies are an efficient means to study disease aetiologies, and may be the only practical means to investigate rare diseases. However, exposure assessment remains problematic. We review the literature on the validity and reliability of common case-control exposure assessment methods: occupational histories, job-exposure matrices (JEMs), self reported exposures, and expert assessments. Given the variable quality of current exposure assessment techniques, we suggest methods to improve assessments, including the incorporation of hygiene measurements: using data from administrative exposure databases; using results of studies identifying determinants of exposure to develop questionnaires; and where reasonable given latency and biological half life considerations, directly measuring exposures of study subjects.

Case-Control Studies↗

Three-body Coulomb problem probed by mapping the Bethe surface in ionizing ion-atom collisions.

The three-body Coulomb problem has been explored in kinematically complete experiments on single ionization of helium by 100 MeV/u C(6+) and 3.6 MeV/u Au(53+) impact. Low-energy electron emission ( E(e)<150 eV) as a function of the projectile deflection theta(p) (momentum transfer), i.e., the Bethe surface [15], has been mapped with Delta theta(p)+/-25 nanoradian resolution at extremely large perturbations ( 3.6 MeV/u Au(53+)) where single ionization occurs at impact parameters of typically 10 times the He K-shell radius. The experimental data are not in agreement with state-of-the-art continuum distorted wave-eikonal initial state theory.

Journal Article↗

Assignment to menopausal status and estimation of age at menopause for women with missing or invalid data--a probabilistic approach with weighting factors in a large-scale epidemiological study.

OBJECTIVE: Gynaecologic surgeries and hormone medication increasingly interfere with the concept of determining menopausal status based on self-reported data about the last menstrual period-an approach frequently applied in epidemiological studies. This analysis compared different approaches of menopausal status determination, including a probabilistic approach that was developed to reduce misclassification of menopausal status. METHODS: Interview and questionnaire data relating to hormone status from about 16,000 German women were used to determine menopausal status using different approaches: menses based, age based, self-assessment based, and a probabilistic approach. RESULTS: Applying strict menses-based criteria, 29.1% of the women were found to be with undetermined menopausal status. The probabilistic approach was applied to determine menopausal status and age at menopause for these women. The proposed approach uses the current age of the women with undetermined menopausal status, and the relative age-dependent frequencies of pre- or postmenopausal status among those with natural menopausal status to calculate weighting factors, which represent the probabilities of being pre- and postmenopausal of each woman previously undetermined. Correspondingly, the missing age at menopause was estimated with the same probabilistic approach. Applying various approaches to determine menopausal status, the ratio of pre- to postmenopausal women differed considerably, ranging from 1.03 to 1.61. In addition, considerable differences were observed with respect to the number of missing values for both menopausal status and age at menopause. CONCLUSION: The probabilistic approach allowed to estimate menopausal status and age at menopause with the advantage that all available information from the entire study population and from the individual is used.

Adult↗

Variations of the asset prices.

The empirical established non-Gaussian behavior of asset price fluctuations is studied using an analytical approach. The analysis is based on a nonlinear Fokker-Planck equation with a self-organized feedback-coupling term, devised as a fundamental model for price dynamics. The evidence, and the analytical form of the memory term, are discussed in the context of statistical physics. It will be suggested that the memory term in leading order offers a power law dependence with an exponent straight theta. The stationary solution of the probability density leads asymptotically to a truncated Lévy distribution, the characteristic exponent beta of which is related to the exponent straight theta by beta=3/theta-1. The empirical data can be reproduced by theta approximately 5/4.

Journal Article↗

Timbre-specific enhancement of auditory cortical representations in musicians.

Neural imaging studies have shown that the brains of skilled musicians respond differently to musical stimuli than do the brains of non-musicians, particularly for musicians who commenced practice at an early age. Whether brain attributes related to musical skill are attributable to musical practice or are hereditary traits that influence the decision to train musically is a subject of controversy, owing to its pedagogic implications. Here we report that auditory cortical representations measured neuromagnetically for tones of different timbre (violin and trumpet) are enhanced compared to sine tones in violinists and trumpeters, preferentially for timbres of the instrument of training. Timbre specificity is predicted by a principle of use-dependent plasticity and imposes new requirements on nativistic accounts of brain attributes associated with musical skill.

Acoustic Stimulation↗

Identification of nucleolin as a glucocorticoid receptor interacting protein.

The glucocorticoid receptor (GR) is a ligand-induced transcription factor which modulates the transcriptional activity of target genes. Full transcriptional activity of GR is achieved with the help of accessory proteins that are able to interact with GR. We have identified a 95-kDa protein by a blotting technique which utilizes a radioactively labeled DNA-bound GR to detect proteins that bind to this complex. Biochemical purification of this protein followed by protein microsequencing resulted in the identification of human nucleolin. In addition we could show that a GR-deletion mutant localizes to the nucleolus, where nucleolin is one of the most abundant proteins. The binding of nucleolin to this deletion mutant was demonstrated by GST-pull-down experiments. We suggest a biological role of nucleolin in binding of GR in the nucleolus.

Animals↗