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K Held

Publications and source records attributed to K Held.

At least 37 records · Page 2Linked to original sources
PubMed2000

Electronic correlations in manganites

The influence of local electronic correlations on the properties of colossal magnetoresistive manganites is investigated. To this end, a ferromagnetic two-band Kondo lattice model is supplemented with the local Coulomb repulsion missing in this model and is analyzed within dynamical mean-field theory. Results for the spectral function, optical conductivity, and the paramagnetic-to-ferromagnetic phase transition show that electronic correlations have drastic effects and may explain some experimental observations.

Journal Article↗
PubMed2000

A method for measuring disulfide reduction by cultured mammalian cells: relative contributions of glutathione-dependent and glutathione-independent mechanisms.

A method is described for measuring bioreduction of hydroxyethyl disulfide (HEDS) or alpha-lipoate by human A549 lung, MCF7 mammary, and DU145 prostate carcinomas as well as rodent tumor cells in vitro. Reduction of HEDS or alpha-lipoate was measured by removing aliquots of the glucose-containing media and measuring the reduced thiol with DTNB (Ellman's reagent). Addition of DTNB to cells followed by disulfide addition directly measures the formation of newly reduced thiol. A549 cells exhibit the highest capacity to reduce alpha-lipoate, while Q7 rat hepatoma cells show the highest rate of HEDS reduction. Millimolar quantities of reduced thiol are produced for both substrates. Oxidized dithiothreitol and cystamine were reduced to a lesser degree. DTNB, glutathione disulfide, and cystine were only marginally reduced by the cell cultures. Glucose-6-phosphate deficient CHO cells (E89) do not reduce alpha-lipoate and reduce HEDS at a much slower rate compared to wild-type CHO-K1 cells. Depletion of glutathione prevents the reduction of HEDS. The depletion of glutathione inhibited reduction of alpha-lipoate by 25% and HEDS by 50% in A549 cells, while GSH depletion did not inhibit alpha-lipoate reduction in Q7 cells but completely blocked HEDS reduction. These data suggest that the relative participation of the thioltransferase (glutaredoxin) and thioredoxin systems in overall cellular disulfide reduction is cell line specific. The effects of various inhibitors of the thiol-disulfide oxidoreductase enzymes (1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), arsenite, and phenylarsine oxide) support this conclusion.

Animals↗
PubMed2000

The long-term effect of external quality assessment on performance in service cytogenetics.

In 1993 a nationwide cytogenetic external quality assessment program (EQA) was initiated in the Federal Republic of Germany. Presently, some 70 laboratories, representing approximately 90% of all cytogenetic diagnostic tests, are participating in the study. Based on the quality assessment scheme of the Association of Clinical Cytogeneticists (1988) in the United Kingdom, quality of chromosome preparation and speed of routine diagnostic services are being evaluated. As a result of continuous external quality assessment, the mean banding level of participating laboratories rose from below 400 bands per haploid set (bphs) in 1994 to approximately 450 bphs in 1999 in prenatal tests and from about 400 to approximately 500 bphs in postnatal tests over the same 5-yr period. The percentage of participants achieving a banding level of 400 bphs or higher rose from approximately 50% to 93% in prenatal tests and from 60% to 96% in postnatal tests. No significant differences were observed in banding scores achieved by private laboratories compared to university institutes. The impact of the assessment of interpretation, reporting, and documentation remains difficult to evaluate. Preliminary data point to a more stringent adherence to ISCN nomenclature in karyotype designation by participants.

Chromosome Aberrations↗
PubMed1998

Radiation-sensitive tyrosine phosphorylation of cellular proteins: sensitive to changes in GSH content induced by pretreatment with N-acetyl-L-cysteine or L-buthionine-S,R-sulfoximine.

PURPOSE: At relatively high concentrations, ie., > 20 mM, N-acetyl-L-cysteine (NAC) scavenges reactive oxygen species produced by ionizing radiation in aqueous solution. Therefore, the ability of NAC to block signal transduction reactions in vivo, has lead to the suggestion that ROS are necessary for the normal propagation of these signals. In this paper we investigate the mechanism by which NAC alters signal transduction in whole cells. RESULTS: Exposing CHO-K1 cells to ionizing radiation results in elevated pp59fyn kinase activity. Moreover, we observe changes in the phosphotyrosine content of multiple cellular proteins, including one prominent phosphotyrosyl protein with a Mr of 85 kDa. Both the radiation-induced changes in pp59fyn kinase activity and the changes in phosphotyrosine content of pp85 were not affected by exposing K1 cells to NAC during the time of irradiation, suggesting that ROS generated extracellularly are not involved in the radiation-induced changes observed in phosphotyrosyl proteins. We also demonstrate that the cell membrane is an effective barrier against negatively charged NAC. Therefore, it seems unlikely that NAC's ability to block signal transduction reactions is related to scavenging of ROS intracellularly. Chronic exposure, ie., 1 h, to 20 mM NAC lead to a twofold elevation in GSH levels and resulted in a 17% decrease in the phosphotyrosine content of pp85 after exposure to 10 Gy. Moreover, pretreatment with L-buthionine-S,R-sulfoximine (BSO) decreased GSH levels and resulted in elevated phosphotyrosine levels in pp85 isolated from irradiated CHO-K1 cells. CONCLUSIONS: Since many signaling molecules contain redox sensitive cysteine residues that regulate enzyme activity, we suggest that the effects of NAC on radiation-induced signal transduction are due to its ability to alter the intracellular reducing environment, and not related to direct scavenging of ROS.

Acetylcysteine↗
PubMed1997

Markov random field segmentation of brain MR images.

We describe a fully-automatic three-dimensional (3-D)-segmentation technique for brain magnetic resonance (MR) images. By means of Markov random fields (MRF's) the segmentation algorithm captures three features that are of special importance for MR images, i.e., nonparametric distributions of tissue intensities, neighborhood correlations, and signal inhomogeneities. Detailed simulations and real MR images demonstrate the performance of the segmentation algorithm. In particular, the impact of noise, inhomogeneity, smoothing, and structure thickness are analyzed quantitatively. Even single-echo MR images are well classified into gray matter, white matter, cerebrospinal fluid, scalp-bone, and background. A simulated annealing and an iterated conditional modes implementation are presented.

Algorithms↗
PubMed1996

[Physical complaints, stress and quality of life of oncologic patients. Effects and patient assessment in inpatient rehabilitation].

AIM: To what extent do cancer patients use an inpatient aftercare programme and how is its effect been estimated by them? How is the progress of "general physical complaints", "psychosocial stress" and "satisfaction with life" in some cases over a period of up to eight months? PATIENTS AND METHODS: To 201 patients with breast or intestinal cancer respectively, who were going to be or had already been admitted to an inpatient aftercare, standardised and unstandardized questionnaire were presented to be filled out at 4 or 5 different dates before and during the programme as well as 3 and 6 months later. RESULTS: Many patients tried to take part in the aftercare programme actively. Even 6 months later 95.6% estimated it as being "successful" and 70% said that there had been a lasting positive effect after the treatment. The "general physical complaints" and "psychosocial stress" grew significantly less during the inpatient aftercare programme and "satisfaction with life" improved. After the treatment these effects were declining again. CONCLUSIONS: The results indicate that many patients, who participate in an inpatient aftercare programme, profit by it directly. As the positive effects partially get lost during the following months, the patients should be prepared more intensely for the time after dismission with its higher level of strain and should get an especially attentive ambulant care at home.

Adaptation, Psychological↗
PubMed1992

The importance of peroxide and superoxide in the X-ray response.

Radiation produces a number of damaging radicals as well as peroxide. The chief cellular protection against these radicals, their secondary reactants and peroxide is the cellular glutathione (GSH), GSH peroxidase, GSH-S-transferase (GSHTase), and catalase enzymes. Inhibition of cellular catalase alone does not enhance the aerobic radiation response because cellular GSH peroxidase is equally effective in reducing peroxide. However, inhibition of GSHTase, and partial inhibition of peroxidase by L-buthionine sulfoximine (LBSO)-linked GSH depletion, results in an increased aerobic radiation response. The major pathway for peroxide reduction is the GSH peroxidase. The enzyme is accountable for 70% inactivation of low peroxide concentrations. Catalase accounts for the remaining inactivation. However, it is difficult to assess the relative contributions of GSHTase and peroxidase to the inactivation of radiation-produced hydroperoxides. Our data suggest that GSH depletion results in the inhibition of cellular GSHTase before it inhibits GSH peroxidase. Therefore, part of the increased aerobic radiation response maybe due to cellular inability to reduce hydroperoxides. Peroxide is not a substrate for GSHTase. However, total inhibition of peroxidase by L-BSO plus N-ethylmaleimide (NEM) treatment maximizes the aerobic radiation response. Total inhibition of GSH-S-transferase and peroxidase would block both peroxide and hydroperoxide reduction.

Catalase↗
PubMed1987

Gamma-glutamyl transferase activity in the amniotic fluid of fetuses with chromosomal aberrations and inborn errors of metabolism.

The activity of gamma-glutamyl transferase (GGT) was measured in amniotic fluid collected between the 16th and 30th weeks of gestation from 81 pregnancies with fetuses affected by chromosomal aberrations, nine with different types of inborn errors of metabolism, two with hemophilia A and one with fragile X syndrome. The GGT activity was compared with that from 1000 normal pregnancies and deliveries resulting in healthy newborns. Contamination of amniotic fluid by blood did not affect the GGT activity. Pathologically decreased activity was found in 25 of 56 amniotic samples from pregnancies with fetal autosomal chromosomal aberrations (44.6%). It was decreased in 15 of 35 pregnancies with fetal trisomy 21 (43%), in 11 of 19 pregnancies with fetal trisomy 18 (58%), in one of three pregnancies with fetal trisomy 13 and in two pregnancies with fetal trisomy 8 and triploidy, respectively. In only three of 16 pregnancies with fetal sex chromosomal aberrations was the GGT activity low. Increased GGT activity was found in three of six pregnancies with unbalanced structurally rearranged karyotypes of the fetuses. Normal GGT activity was observed in all nine amniotic fluid samples from pregnancies with fetuses affected with different forms of inborn errors of metabolism diseases, in the two pregnancies with hemophilia A and in the pregnancy with a male fetus with fragile X syndrome. These and earlier findings indicate that the GGT activity in amniotic fluid is mostly decreased in pregnancies with severe fetal developmental abnormalities, such as autosomal chromosomal aberrations, which could possibly be secondary to an alteration of the microvillar transport system of GGT to the amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1987

The hydrodynamically balanced system: a novel principle of controlled drug release.

Madopar HBS (125 mg) is a controlled-release dosage form with 100 mg L-dopa and 25 mg benserazide. The 'hydrodynamically balanced system' (HBS) used for this novel dosage form of Madopar is a dosage form which, when in contact with gastric fluid and after dissolution of the gelatine shell of the capsule, forms a mucous body and a bulk density of less than 1 and releases the drug(s) at a desired rate whereas the dosage form remains in the stomach for a prolonged period of time. Drugs--in the present case L-dopa and benserazide--are released through the hydrated layer by diffusion principle. This system is valuable for drugs which are soluble at lower pH. By varying the composition of the excipients, desired release rates can be achieved. The in vitro dissolution rate of Madopar HBS formulation is as follows: L-dopa t75% = about 6 h and benserazide t75% = about 4 h. The floating behavior was tested in an in vitro test. These in vitro floating properties could be confirmed in man and were investigated in 10 healthy volunteers by means of gamma camera measurements using a poly-marker technique carried out in connection with a Valium CR study. It is expected that this novel drug delivery system proffers a valuable dosage form which delivers the drug at a specific rate allowing a better control of fluctuations in parkinsonian patients.

Administration, Oral↗
PubMed1978

Investigation of copulative activity in male rats in chronic experiment.

Copulative activity of 28 male Wistar rats was investigated for one year at 6 to 8 day intervals. Metholds have been worked out for the selection of sexually active males. It was found that it is possible to investigate copulative activity permanently in a selected population of male rats. The sexual activity index number of intromissions/time of ejaculation can be applied to the 15-minute test. In order to evaluate individual differences observed during the experiments, the ratio positive experiments/all experiments has been used. During a one-year experimental period (791 experiments altogether) mean latency time was 56'', and that of the ejaculation 7'10''. The average number of intromissions was 7.89, and that of attempts 3.41. Ejaculation occurred 575 times. The average sexual activity index was 1.1. There was no seasonal fluctuation in copulative activity.

Animals↗