Search PubMed⌕ Search

Biomedical subjects

T Schmidt

Publications and source records attributed to T Schmidt.

At least 55 records · Page 3Linked to original sources

Glass classification by linear discriminant analysis of LA-ICP-MS data.

The classification of pharmaceutical and common glasses (ampoules, infusion bottles, cylinders, lead crystal and bottle glass) has been performed means by of chemometric methods. For this purpose intensity data of glass examinations received by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) were applied. A Nd:YAG laser with 10 Hz repetition rate in the Q-switch mode at its 4th harmonic (266 nm) was used to get mass spectrometric data of the glasses. 13 isotopes (= variables) were used for measurements (7Li, 11B, 23Na, 24Mg, 27Al, 28Si, 39K, 42Ca, 47Ti, 57Fe, 123Sb, 137Ba, 207Pb). The glass samples represented four types of glasses: 1. borosilicate glass (type "Duran") 2. borosilicate glass (type "Fiolax") 3. soda-lime glass 4. lead glass. Calculations were made by using the SAS statistical software. All results were obtained on the assumption that the underlying data are normally distributed. By applying linear discriminant data analysis a classification of all types of the glasses was possible (13 variables included). The use of the method of "stepwise discriminant analysis" reduced the minimal required number of variables to eight. All types of glasses could be distinguished faultlessly. Besides a graphic system consisting of the isotopes 24Mg-47Ti-137Ba was developed. By means of this system optical distinction of glass classes was possible. The developed method allows to distinguish several types of pharmaceutical and common glasses on the basis of intensity data of mass spectrometric measurement without calibration experiments and linear regression.

Algorithms↗

Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry.

An analytical method is presented enabling the determination of nine neutral pharmaceuticals in groundwater, and for most of the compounds, in rivers and wastewater down to the lower ng/l range. The analytes belong to different medicinal groups such as antiphlogistics, psychiatric drugs and antidiabetics. Samples are enriched using solid-phase extraction (SPE) with RP-C18ec material. Analysis is performed by liquid chromatography with detection by electrospray tandem MS. Mean recoveries generally exceed 80% in groundwater, and the quantification limits are down to 50 ng/l in wastewater and down to 10 ng/l in groundwater. Losses were observed to occur either from ion suppression in the electrospray ionisation or SPE. Losses for all compounds could not be compensated for by the surrogate standard dihydrocarbamazepine. In raw municipal wastewater, concentration levels were detected for caffeine up to 147 microg/l and for propyphenazone up to 1.3 microg/l.

Chromatography, High Pressure Liquid↗

Preparation and crystal structure of the ternary uranium rare Earth antimonides (U(2/3)R(1/3))Sb(2) and (U(1/2)R(1/2))(3)Sb(7) with mixed U/R occupancy of the metal sites and a variety of antimony polyanions.

The ternary antimonides (U(2/3)R(1/3))Sb(2) (R = Y, Ce-Nd, Sm, Gd-Tm) and (U(1/2)R(1/2))(3)Sb(7) (R = Y, Gd-Ho) have been prepared by reaction of the uranium antimonide USb(2) with the corresponding rare earth antimonides RSb(2) and an excess of elemental antimony at high temperatures. The crystal structure of the isotypic series (U(2/3)R(1/3))Sb(2) has been determined from single-crystal X-ray data of (U(0.675(9))Gd(0.325(9)))Sb(2). It is isotypic with PbCl(2): Pnma, Z = 4, a = 754.6(1), b = 419.6(1), c = 1025.7(3) pm. The compounds of the other series crystallize with a new structure type, which has been determined for (U(0.49(1))Ho(0.51(1)))(3)Sb(7): Immm, Z = 4, a = 410.1(1), b = 1447.7(3), c = 1821.2(5) pm. In both structures, the metal positions have mixed occupancy and high coordination numbers. Both structures contain numerous weak Sb-Sb bonds, thus forming a band of antimony atoms in the structure of (U(2/3)Gd(1/3))Sb(2) and a chain and a three-dimensionally infinite network of antimony atoms in the structure of (U(1/2)Ho(1/2))(3)Sb(7). Analyses of the Sb-Sb bonding within the antimony polyanions on the basis of bond-length bond-strength considerations indicate that the uranium atoms have mixed or intermediate +3/+4 valence in these compounds. The structure of (U(1/2)Ho(1/2))(3)Sb(7) may be considered as a defect variant of the structure of Ce(6)MnSb(15).

Journal Article↗

Functional characterization of the human Huntington's disease gene promoter.

The genetic basis of neurodegeneration in Huntington's disease (HD) has been identified as a (CAG)(>37) repeat expansion in a gene of unknown function. Interestingly, patients with the same expanded (CAG)(n) repeat length may have markedly different ages at onset. Based on experiences in animal models the level of expression might be one of the modifying factors. To gain insight into the regulation of the human HD gene we functionally analyzed 2266 bp of the HD gene promoter region. This region lacks a TATA and a CAAT box, is GCrich, and it has several consensus sequences for SP1, AP-2 and AP-4 binding sites. The stretch between nucleotides -49 and -198 relative to the first ATG is highly conserved between human and rodents and it harbors several potential binding sites for transcription factors. We analyzed deletion mutants fused with the chloramphenicol acetyltransferase (CAT) reporter gene in transfected, huntingtin expressing neuronal (NS20Y) and non-neuronal (CHO) cell lines. Partial deletion of the evolutionarily conserved part of the promoter significantly reduces the activity in both neuronal and non-neuronal cells indicating that the core promoter activity is located between nucleotides -221 and 4, relative to the +1 translation start site. Binding affinities of DNA-protein interactions were defined by electrophoretic mobility shift assays and the protected nucleotide positions were determined by DNase I footprinting.

Age of Onset↗

Spatial variation of au coverage as the driving force for nanoscopic pattern formation.

Au induced faceting of a 4 degrees vicinal Si(001) surface was studied with chemical resolution using soft x-ray photoemission electron microscopy. For the first time a direct and quantitative determination of the local Au coverage in situ and during deposition was possible. Au atoms, necessary for the expansion of (001) terraces, are accummulated from a lattice gas, resulting in a phase separation between Au enriched terraces and Au depleted step bunches. During a second stage Au also adsorbs on the step bunches and transforms them into (119) facets. A simple Monte Carlo simulation shows that the initial coverage difference between terraces and bunches determines the regularity of the formed mesoscopic grating.

Journal Article↗

Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue.

Prostate tissue was obtained from 22 radical prostatectomies (performed for clinical management of prostate carcinoma) immediately after surgery. A small piece of tissue was fixed immediately in formalin and used for routine histology while a second piece was frozen in OCT and used for immuno-histochemistry. Another small piece was used for isolation of epithelial and stromal cells. The remainder of the tissue was cut into 2 x 2 mm pieces and incubated in organ culture for 8 days. In organ culture, non-malignant, basal epithelial cells underwent a proliferative response. This was accompanied by de-differentiation of glandular structures and by migration of epithelial cells across the surface of the tissue. Erosion of the basement membrane could also be seen in places, but was not widespread. Invasion of epithelial cells into the adjacent stroma was not evident. Production of matrix metalloproteinases (MMPs) with gelatinolytic activity or collagenolytic activity was assessed in organ culture and compared to expression patterns in fresh tissue. MMP-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) were undetectable or low in fresh tissue specimens. Both enzymes were detected in organ culture and both increased over time. Even after 6 days, however, there was only a low level of gelatin-hydrolytic activity and no measurable collagen-hydrolytic activity. In past studies we used organ cultures of normal skin and malignant skin tumours (basal cell carcinomas) to help elucidate the role of collagenolytic and gelatinolytic MMPs in epithelial cell invasion (Varani et al, 2000). Compared to MMP levels observed in skin, levels of these enzymes in prostate are low. The low level of collagenolytic and gelatinolytic MMPs in fresh prostate tissue and in organ-cultured prostate tissue may help explain why there is little tissue destruction in many primary prostate tumours and why the majority of such tumours remain confined to the prostate for extended periods.

Collagen↗

Structures of bovine glutamate dehydrogenase complexes elucidate the mechanism of purine regulation.

Glutamate dehydrogenase is found in all organisms and catalyses the oxidative deamination of l-glutamate to 2-oxoglutarate. However, only animal GDH utilizes both NAD(H) or NADP(H) with comparable efficacy and exhibits a complex pattern of allosteric inhibition by a wide variety of small molecules. The major allosteric inhibitors are GTP and NADH and the two main allosteric activators are ADP and NAD(+). The structures presented here have refined and modified the previous structural model of allosteric regulation inferred from the original boGDH.NADH.GLU.GTP complex. The boGDH.NAD(+).alpha-KG complex structure clearly demonstrates that the second coenzyme-binding site lies directly under the "pivot helix" of the NAD(+) binding domain. In this complex, phosphates are observed to occupy the inhibitory GTP site and may be responsible for the previously observed structural stabilization by polyanions. The boGDH.NADPH.GLU.GTP complex shows the location of the additional phosphate on the active site coenzyme molecule and the GTP molecule bound to the GTP inhibitory site. As expected, since NADPH does not bind well to the second coenzyme site, no evidence of a bound molecule is observed at the second coenzyme site under the pivot helix. Therefore, these results suggest that the inhibitory GTP site is as previously identified. However, ADP, NAD(+), and NADH all bind under the pivot helix, but a second GTP molecule does not. Kinetic analysis of a hyperinsulinism/hyperammonemia mutant strongly suggests that ATP can inhibit the reaction by binding to the GTP site. Finally, the fact that NADH, NAD(+), and ADP all bind to the same site requires a re-analysis of the previous models for NADH inhibition.

Adenosine Diphosphate↗

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice.

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.

Journal Article↗

Statistical analysis of single-molecule colocalization assays.

In chemical assays, specific molecular recognition events result in close physical proximity of two molecular species, e.g., ligands and receptors. Microscopy techniques that are able to image individual molecules allow for achieving a positional accuracy far beyond the resolution limit Therefore, independent position determination, e.g., by dual-color microscopy, becomes possible, permitting determination of intermolecular distances beyond the resolution limit. Nonzero measured distances occur due to experimental inaccuracies in case of a recognition event or due to accidental close proximity between ligand-receptor pairs. Using general statistical considerations, finite measured distances between single ligand-receptor pairs are directly translated into probabilities for true molecular recognition or mere accidental proximity. This enables a quantitative statistical analysis of single recognition events. It is demonstrated that in a general assay, even in the presence of strong unspecific background, the probability for a certain diagnosis and a measure for its reliability can be extracted from the observation of a few binding events. The power of the method is demonstrated at the example of a single-molecule DNA hybridization assay. Our findings are of major importance for future assay miniaturization and assaying with minute amounts of analyte.

Journal Article↗

Energy dependence of quasiparticle relaxation in a disordered fermi liquid.

A spectroscopic method is applied to measure the inelastic quasiparticle relaxation rate in a disordered Fermi liquid. The quasiparticle relaxation rate gamma is deduced from the magnitude of fluctuations in the local density of states, which are probed using resonant tunneling through a localized impurity state. We study its dependence on the excitation energy E measured from the Fermi level. In a disordered metal (heavily doped GaAs) we find that gamma~E3/2 within the experimentally accessible energy interval, in agreement with the Altshuler-Aronov theory for electron-electron interactions in diffusive conductors.

Journal Article↗

Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously arising in the colon and in the lung: report of a case.

zone B cell lymphoma of mucosa-associated lymphoid tissue type according to the Revised European American Lymphoma classification). Other mucosa-associated lymphoid tissue-type lymphomas arise in the salivary glands, thyroid gland, and in the lung (bronchus-associated lymphoid tissue). Here, we report the first case of a monoclonal mucosa-associated lymphoid tissue lymphoma with simultaneous manifestation in the colonic and bronchial mucosa in a 62-year-old patient. With mitoxantrone, chlorambucil, and prednisone polychemotherapy, a complete year-long remission was achieved.

Antineoplastic Combined Chemotherapy Protocols↗

[Selection of subjects: a problem of clinical trials in traumatology. Selection effects and the problem of representation as exemplified by a prospective randomized trial on whiplash injuries].

INTRODUCTION: The internal and external validity of studies is endangered by many factors, such as selection of subjects for inclusion. Selection bias itself is a major problem, but remains unmentioned and probably unexamined in the majority of published clinical trials in traumatology. AIM OF THE STUDY: The aim of this investigation was to detect effects of subject selection which occurred during our own prospective intervention study. The clinical trial compared subjects with whiplash injury who were either treated by early mobilization or immobilization (soft collar). MATERIAL AND METHODS: Source population, eligible subjects, study participants and final study participants were compared for differences on various items like age, gender and further sociodemographic as well as crash related factors and clinical findings. RESULTS: Between 21.08.1997 and 30.04.1999 a total of 732 patients was examined and treated after whiplash in our trauma department. The options for inclusion were met by 453 patients. While 346 escaped from the study, 107 agreed to participate. Of these another 39 patients dropped out of the study. Selection effects were detected on two different levels, leading to distinct statistical procedures from those proposed in the study protocol. CONCLUSIONS: Uncontrolled selection effects could undermine the interpretability of the results of clinical trials. Awareness of selection effects is mandatory regarding the applicability of these results to subjects, other than those in the group of the final study participants.

Humans↗

Single-molecule imaging of l-type Ca(2+) channels in live cells.

L-type Ca(2+) channels are an important means by which a cell regulates the Ca(2+) influx into the cytosol on electrical stimulation. Their structure and dynamics in the plasma membrane, including their molecular mobility and aggregation, is of key interest for the in-depth understanding of their function. Construction of a fluorescent variant by fusion of the yellow-fluorescent protein to the ion channel and expression in a human cell line allowed us to address its dynamic embedding in the membrane at the level of individual channels in vivo. We report on the observation of individual fluorescence-labeled human cardiac L-type Ca(2+) channels using wide-field fluorescence microscopy in living cells. Our fluorescence and electrophysiological data indicate that L-type Ca(2+) channels tend to form larger aggregates which are mobile in the plasma membrane.

Bacterial Proteins↗

Autofluorescent proteins in single-molecule research: applications to live cell imaging microscopy.

The spectral and photophysical characteristics of the autofluorescent proteins were analyzed and compared to flavinoids to test their applicability for single-molecule microscopy in live cells. We compare 1) the number of photons emitted by individual autofluorescent proteins in artificial and in vivo situations, 2) the saturation intensities of the various autofluorescent proteins, and 3) the maximal emitted photons from individual fluorophores in order to specify their use for repetitive imaging and dynamical analysis. It is found that under relevant conditions and for millisecond integration periods, the autofluorescent proteins have photon emission rates of approximately 3000 photons/ms (with the exception of DsRed), saturation intensities from 6 to 50 kW/cm2, and photobleaching yields from 10(-4) to 10(-5). Definition of a detection ratio led to the conclusion that the yellow-fluorescent protein mutant eYFP is superior compared to all the fluorescent proteins for single-molecule studies in vivo. This finding was subsequently used for demonstration of the applicability of eYFP in biophysical research. From tracking the lateral and rotational diffusion of eYFP in artificial material, and when bound to membranes of live cells, eYFP is found to dynamically track the entity to which it is anchored.

Bacterial Proteins↗

Magnetic resonance urography in children: evaluation of suspected ureteral ectopia in duplex systems.

PURPOSE: We evaluate the diagnostic accuracy of magnetic resonance urography in children with suspected ectopic ureters and ureteroceles in duplex systems. MATERIALS AND METHODS: A total of 14 children 4 weeks to 8 years old with a total of 18 duplex systems underwent magnetic resonance urography using a 1.5 tesla scanner. After injection of low dose furosemide, half-Fourier rapid acquisition with relaxation enhancement images were obtained for T2-weighted static fluid magnetic resonance urography. Respiratory gated 3-dimensional gradient echo images were acquired for T1-weighted excretory magnetic resonance urography 5 to 30 minutes after intravenously administered gadolinium. RESULTS: All magnetic resonance examinations were successfully performed without sedation. The diagnostic accuracy of T1-weighted excretory magnetic resonance urography depended on the renal function. Twelve duplex systems with a normal excretory function, including 6 bifid ureters and 6 upper moieties with inferomedial ectopic ureters, were analyzed correctly with the exception of a 6 mm. ureterocele in 1 case. In 6 duplex systems with poor or nonfunctioning upper moieties ectopic ureters were only demonstrated on T2-weighted magnetic resonance urograms. CONCLUSIONS: Respiratory gated excretory and static fluid magnetic resonance urography complement each other in the evaluation of duplex systems in children and provide high accuracy in the evaluation of suspected ectopic ureters and ureteroceles.

Child↗

Normal TCRbeta transcription and recombination in the absence of the Jbeta2-Cbeta2 intronic cis element.

The developmental regulation of antigen receptor gene transcription and recombination are mediated by cis regulatory elements. At the T cell receptor beta chain locus (TCRbeta), two DNase I hypersensitive sites within the Jbeta2-Cbeta2 intron contained binding sites for NF-kappaB and additional nuclear factors and were postulated to be involved in controlling TCRbeta transcription and V(D)J recombination. To test this possibility, we deleted these elements from the mouse genome by homologous recombination and assayed the effect on transcription of both the germline and rearranged TCRbeta locus, and on TCRbeta rearrangement in T and B lymphocytes. We found that TCRbeta transcription and V(D)J recombination and T cell development were normal in these mutant mice. Therefore, the Jbeta2-Cbeta2 intronic elements are dispensable for TCRbeta assembly and function.

Animals↗

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies with longitudinal follow-up in the second trial. SETTING: Academic Department of Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.

Abortion, Spontaneous↗