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Biomedical subjects

A Freund

Publications and source records attributed to A Freund.

At least 19 recordsLinked to original sources
PubMed2006

A kinetic study of lipase-catalyzed reversible kinetic resolution involving verification at miniplant-scale.

Lipase-catalyzed kinetic resolution of racemates is a popular method for synthesis of chiral synthons. Most of these resolutions are reversible equilibrium limited reactions. For the first time, an extensive kinetic model is proposed for kinetic resolution reactions, which takes into account the full reversibility of the reaction, substrate inhibition by an acyl donor and an acyl acceptor as well as alternative substrate inhibition by each enantiomer. For this purpose, the reversible enantioselective transesterification of (R/S)-1-methoxy-2-propanol with ethyl acetate catalyzed by Candida antarctica lipase B (CAL-B) is investigated. The detailed model presented here is valid for a wide range of substrate and product concentrations. Following model discrimination and the application of Haldane equations to reduce the degree of freedom in parameter estimation, the 11 free parameters are successfully identified. All parameters are fitted to the complete data set simultaneously. Six types of independent initial rate studies provide a solid data basis for the model. The effect of changes in substrate and product concentration on reaction kinetics is discussed. The developed model is used for simulations to study the behavior of reaction kinetics in a fixed bed reactor. The typical plot of enantiomeric excess versus conversion of substrate and product is evaluated at various initial substrate mixtures. The model is validated by comparison with experimental results obtained with a fixed bed reactor, which is part of a fully automated state-of-the-art miniplant.

Enzymes, Immobilized↗
PubMed2003

Geometric scaling in inclusive eA reactions and nonlinear perturbative QCD.

We report on geometric scaling in inclusive eA scattering data from the NMC and E665 experiments. This scaling and nuclear shadowing follows the pattern expected from nonlinear perturbative QCD for zero impact parameter at sufficiently small x(bj) and is compatible with geometric scaling in ep.

Journal Article↗
PubMed2003

Diffractive refractive optics: the possibility of sagittal focusing in Laue-case diffraction.

The sagittal deviation of a Laue-diffracted X-ray beam caused by the inclination of an exit crystal surface with respect to an entrance crystal surface has been studied both theoretically and experimentally. The use of this effect for sagittal focusing of X-ray synchrotron radiation diffracted by a Laue crystal is suggested. The focusing is based on the refraction effect due to the parabolic profile of an exit or/and entrance surface. The crystal is not bent. In order to achieve a reasonable focusing distance, the crystal should be cut asymmetrically. The experiment was performed at beamline BM5 at the ESRF.

Journal Article↗
PubMed2003

Exclusive annihilation pp-->gammagamma in a generalized Parton picture.

Exclusive proton-antiproton annihilation into two photons at large s ( approximately 10 GeV2) and /t/,/u/ approximately s can be described by a generalized parton picture analogous to the "soft mechanism" in wide-angle real Compton scattering. The two photons are emitted in the annihilation of a single fast quark and antiquark. The matrix element describing the transition of the pp system to a qq pair can be related to the timelike proton elastic form factors as well as to the quark/antiquark distributions measured in inclusive deep-inelastic scattering. The reaction could be studied with the proposed 1.5-15 GeV high-luminosity antiproton storage ring (HESR) at GSI.

Journal Article↗
PubMed2001

Sagittal focusing of synchrotron radiation diffracted on the walls of a longitudinal hole drilled into a single-crystal monochromator.

A very simple method of sagittal focusing of X-ray synchrotron radiation is presented. A special ray-tracing program which utilizes the diffraction-refraction effect is developed. It is demonstrated both by ray-tracing simulations and by an experiment whereby a reasonably good sagittal concentration of 8 keV synchrotron radiation may be achieved by diffraction on the walls of a cylindrical hole drilled into an Si crystal. The holes were drilled parallel to the (111) planes and their diameter, 1 mm, was chosen so that the focusing distance fits the geometrical arrangement of beamline BM5 at the ESRF. Two such crystals have been used in a dispersive and non-dispersive arrangement. The better result was achieved using the dispersive arrangement. The intensity at the centre of the focus is increased by five times with respect to unfocused radiation. Excellent agreement exists between the ray-tracing simulations and experimental results.

Journal Article↗
PubMed2001

Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells.

The rate of ara-cytosine triphosphate (ara-CTP) accumulation and its retention has been correlated with 1-beta-D-arabinofuranosylcytosine (ara-C)-mediated toxicity and clinical outcome in childhood and adult leukemia. We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine (F-ara-A) and hydroxyurea (HU) enhanced ara-CTP levels in two human myeloid (HL-60, CMK) and two lymphoblastic leukemia cell lines (MOLT-4, BLIN-1) and also in blasts from 28 children with acute leukemia (AML: 14, ALL: 14). Incubation experiments carried out with cell lines showed F-ara-A and HU to be equipotent in increasing ara-CTP levels. The highest increase was observed in HL-60 cells whereas preincubation had no modulatory effect in MOLT-4 cells. Accordingly, modulation of intracellular ara-CTP levels differed between the subtypes of childhood acute leukemia: whereas in T-ALL (five) preincubation with F-ara-A and HU had no effect on intracellular ara-C metabolism, increased ara-CTP levels were seen in some cases of pre-B-ALL (seven). In myelogenous blasts (12) clinically relevant enhancement of ara-C toxification was regularly obtained with both, F-ara-A (1.9-fold) and HU (1.5-fold). In conclusion, our data suggest that combinations of ara-C and ribonucleotide reductase inhibitors are apt to increase ara-CTP levels depending on the individual cell type and its sensitivity towards ara-C modulators.

Adult↗
PubMed1999

All-trans-retinoic acid increases cytosine arabinoside cytotoxicity in HL-60 human leukemia cells in spite of decreased cellular ara-CTP accumulation.

BACKGROUND: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ara-C. To investigate the mechanism of this sensitisation, the hypothesis was tested that ATRA augments cellular ara-CTP levels in human-derived myelogenous leukemia HL-60 cells. MATERIALS AND METHODS: The effect of ATRA and 13-cis-retinoic acid on ara-CTP accumulation and ara-C-induced apoptosis was studied. Ara-CTP levels were measured by high-performance liquid chromatography (HPLC), cytotoxicity by the tetrazolium (MTT) assay, and apoptosis by occurrence of DNA fragmentation (gel electrophoresis), cell shrinkage and DNA loss (flow cytometry). RESULTS: Pretreatment of HL-60 cells with ATRA (0.01-1 microM) caused a significant decrease in intracellular ara-CTP levels; e.g., incubation for 72 hours with ATRA 1 microM prior to one hour ara-C 10 microM reduced ara-CTP levels to 41% +/- 4% of control. Similar results were obtained after preincubation with 13-cis-retinoic acid. In spite of decreased ara-CTP levels, the cytotoxicity of the combination was supraadditive and ATRA augmented ara-C-induced apoptosis. CONCLUSION: At therapeutically relevant concentrations ATRA increased ara-C cytotoxicity and ara-C induced apoptosis but this augmentation is not the corollary of elevated ara-CTP levels. The feasibility of ara-C treatment optimisation via strategies other than those involving elevation of ara-CTP levels should be investigated further.

Analysis of Variance↗
PubMed1998

A scattering filter for energy-dispersive optics.

A filtering technique to remove parasitic scattering from X-ray absorption spectra that are acquired in energy-dispersive mode has been developed and tested at the European Synchrotron Radiation Facility. The improved set-up removes small-angle scattering of the sample or the windows of sample cells which may spoil the energy resolution or reduce the intensity of prominent features in the absorption spectrum, such as the white line at the Pt L(III) edge. The sample is placed behind the curved monochromator and between two plane perfect crystals in the Bonse-Hart configuration. The dispersion of the Bonse-Hart double-crystal camera is matched to the dispersion of the curved monochromator by inclining the scattering planes of the two optical elements against each other.

Journal Article↗
PubMed1998

Design optimization of a flexural hinge-based bender for X-ray optics.

This paper presents a parameter study and design optimization of a flexural hinge-based bender by use of finite-element modelling and analytical formulation. The relationship between the mirror shape and the driving forces, the so-called bender driving equation, is established. Various parameters are investigated: the material properties, the geometrical parameters, the stress and deformation of the mirror and flexural hinge, the residual slope error of the mirror, and the resolution required for the actuators. Analysis results have been compared with test results for a prototype bender and a silicon mirror (170 x 40 x 10 mm). Both analysis and test results confirm the microradian accuracy of the bent mirror. Finally, a bender design for short-bending-radius applications is also presented.

Journal Article↗
PubMed1998

Augmentation of 1-beta-D-arabinofuranosylcytosine (Ara-C) cytotoxicity in leukaemia cells by co-administration with antisignalling drugs.

The ribonucleotide reductase inhibitors hydroxyurea (HU), arabinosyl-2-fluoroadenine (F-Ara-A) and 2-chlorodeoxyadenosine (2-CdA) and the antisignalling drugs all-trans retinoic acid (ATRA), staurosporine and quercetin have been reported to enhance the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C). We tested the hypothesis that the ara-C-sensitising potency of the antisignalling agents is equipotent with that of the ribonucleotide inhibitors. The cytotoxicity, determined by the 3-(4,5 dimethylthiazol-2-yl-)5 diphenyltetrazolium bromide (MTT) assay, of combinations of ara-C with the agents named above was compared in the leukaemia cell lines HL-60, ara-C-resistant HL-60 (HL-60/ara-C) and U937. Furthermore, a range of protein tyrosine kinase inhibitors, genistein, CGP 52411, tyrphostin A48 and nordihydroguaiaretic acid (NDGA), for which ara-C-sensitisation has hitherto not been described, were included in the study. All three cell types acquired increased sensitivity to ara-C when co-incubated with HU or ATRA, but their ara-C sensitivity was not affected by quercetin or genistein. 2-CdA, CGP 52411, tyrphostin A48, staurosporine and NDGA were active as sensitisers against ara-C in HL-60 cells, CGP 52411 and tyrphostin A48 also in HL-60/ara-C cells, and 2-CdA, staurosporine and NDGA also in U937 cells. F-Ara-A increased ara-C toxicity in HL-60/ara-C and U937 cells. To address the mechanism of the observed sensitisation, the influence of agents with ara-C-sensitising properties on ara-C-induced apoptosis was investigated in HL-60 cells as measured by cell shrinkage, DNA loss and DNA fragmentation. HU, ATRA, tyrphostin A48 and NDGA augmented apoptosis induced by ara-C as assessed by all three indicators. CGP 52411 decreased the effect of ara-C on apoptotic indicators after incubation for 4 h, but not after 12 h. The results suggest that ATRA, CGP 52411, tyrphostin A48, staurosporine and NDGA may be suitable alternatives to the clinically applied ribonucleotide reductase inhibitors as modifiers of ara-C cytotoxicity in the treatment of acute myeloid leukaemia.

Antimetabolites, Antineoplastic↗
PubMed1998

Bilateral oedema of the basal ganglia in an echovirus type 21 infection: complete clinical and radiological normalization.

A 4-year-old girl with bilateral striatal oedema in association with an echovirus type 21 infection is reported. In the course of a prolonged upper respiratory-tract infection, the patient developed muscular hypotonia, resting tremor, ataxia, sleepiness, hyperaesthesia, and indistinct speech. T2-weighted cranial MRI revealed bilateral oedema of the basal ganglia and the cerebellar peduncles. At follow-up after 3 months MRI changes and clinical symptoms had fully resolved.

Basal Ganglia↗
PubMed1997

The Y1 antagonist BIBP 3226 inhibits potentiation of methoxamine-induced vasoconstriction by neuropeptide Y.

We investigated the interaction of neuropeptide Y (NPY) with the alpha 1-adrenoceptor agonist, methoxamine, in control of mean arterial pressure, renovascular resistance and mesenteric vascular resistance in anaesthetized rats. Infusion of 3.0 but not 0.3 microgram/kg/min NPY enhanced the elevations of all three haemodynamic parameters caused by bolus injections of methoxamine (10-100 micrograms/kg). These enhancements largely involved a prolongation of the methoxamine effects. While infusion of the Y1 NPY receptor-selective antagonist, BIBP 3226 (10 micrograms/kg/min), alone did not alter methoxamine-induced vasoconstriction, it inhibited the potentiation by NPY. We conclude that NPY can potentiate methoxamine-induced vasoconstriction in vivo. This is mediated predominantly, if not exclusively, via the Y1 receptor. Endogenously released NPY does not appear to reach sufficient concentrations to cause tonic systemic vasoconstriction or potentiation thereof in the anaesthetized rat.

Animals↗
PubMed1997

A hypermedia tutorial for cross-sectional anatomy: HyperMed.

Modern imaging techniques like computer tomography (CT) and nuclear magnetic resonance (MR) imaging have become essential in clinical diagnostics and also in teaching gross anatomy to medical students. As a consequence, special classes in (cross)-sectional anatomy are being added to the curriculum in many anatomical institutions. Since institutional budgets often do not allow extensive supervision beyond the very limited time frame of traditional courses in gross anatomy, a computer-based hypermedia tutorial (HyperMed) was created and integrated into the teaching program of the Institute of Anatomy at Essen University. HyperMed offers two components, one for authors (e.g. teachers who can customize the contents of the program) and a second for users (e.g. students). In the present version, digital cross-sectional human images have been edited. The relevant anatomical structures in these images have been marked, named, and linked to additional information and figures (in particular schematic figures and CT images). Users can obtain information at different levels: (1) index-based retrieval, (2) navigational retrieval (on inspecting cross-sectional images the user is asked to identify structures) and (3) a history list enabling users to go back to any previous point of navigation. HyperMed was first tested in the winter terms 1995/1996 and 1996/1997 during classes on cross-sectional anatomy which are a supplement to the traditional dissection course of the Institute of Anatomy, University Essen. It was well received by the students who found it a helpful adjunct to learning cross-sectional anatomy.

Anatomy, Cross-Sectional↗
PubMed1991

Assessing daily management of childhood diabetes using 24-hour recall interviews: reliability and stability.

Conducted 24-hr recall interviews concerning daily diabetes management with seventy-eight 6- to 19-year-old patients and their parents. Patients and parents were interviewed independently nine times over 3 months. Data obtained were used to construct 13 adherence measures. All measures yielded statistically significant estimates of parent-child concordance. Parent-child agreement was higher for weekday versus weekend behaviors and when based on nine versus three interviews. For the sample as a whole, parent-child concordance remained stable over the course of the study. Compared to the older patients, the 6- to 9-year-olds exhibited poorer parent-child agreement on measures involving time (e.g., injection and exercise-duration measures). This deficit disappeared, however, as the children became more practiced with the interview procedure. The dietary and glucose-testing measures exhibited moderate stability over the 3-month study. Lower stability estimates were obtained for the exercise and injection measures.

Activities of Daily Living↗
PubMed1990

Adherence-health status relationships in childhood diabetes.

Used 24-hr recall interviews to assess adherence in a sample of seventy-eight 6- to 19-year-olds with insulin-dependent diabetes mellitus over a 3-month period. Thirteen adherence measures were quantified and grouped into six adherence factors (Injection, Exercise, Diet Type, Testing/Eating Frequency, Calories Consumed, and Concentrated Sweets). Prevailing glucose levels over a 2- to 3-month interval were indexed by glycosylated hemoglobin A1c (HA1c) and glycosylated serum protein (GSP) assays. Fasting triglycerides (TRIG) and total cholesterol (CHOL) assays were used to estimate lipid metabolism. Adolescents were generally less adherent than their young counterparts. Using hierarchical multiple-regression techniques, HA1c and GSP were not reliably predicted by most of the adherence factors; only Calories Consumed showed any predictive power. No significant regression equations emerged for CHOL. In contrast, TRIG was significantly associated with five of the six adherence factors; in all cases, adherence interacted with the patients' metabolic status (as defined by HA1c) at study entry, suggesting that adherence had different effects for youngsters in good versus poor diabetes control.

Adolescent↗