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Biomedical subjects

Claudia Müller

Publications and source records attributed to Claudia Müller.

16 recordsLinked to original sources
PubMed2006

Positive and negative religious coping in German breast cancer patients.

A growing interest has been focusing on the relationship between religious coping and psychosocial adjustment among cancer patients. However, previous research mostly has not differentiated between positive and negative components of religious coping. The current cross-sectional study investigated the role of both positive religious coping, i.e., a confident and constructive turning to religion, and negative religious coping, i.e., religious struggle and doubt, in a sample of 156 German breast cancer patients. Participants were assessed upon admission to an inpatient rehabilitation program. In addition to religious coping, two basic nonreligious coping styles (depressive coping and active problem-focused coping) and psychosocial adjustment (anxiety and depression) were measured. Major research questions concerning the mediating role of nonreligious coping and the relative predictive power of positive and negative religious coping were primarily addressed using structural equation modeling. Results indicated that the relationship between religious coping and psychosocial outcomes was completely mediated by nonreligious coping, whereby only depressive coping and not active problem-focused coping proved to be a mediating variable. Positive and negative religious coping were somewhat positively related to each other; their (indirect) predictive power on psychosocial adjustment was identical though in an opposite direction. All in all, the results correspond to previous Anglo-American research. There are, however, some discrepancies which may be due to the specific religious-cultural background in Germany.

Adaptation, Psychological↗
PubMed2006

Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a rare complication of liver diseases of different etiologies and may indicate a poor prognosis. Therefore, a simple non-invasive screening method to detect HPS would be highly desirable. In this study pulse oximetry was evaluated to identify patients with HPS. METHODS: In 316 consecutive patients with liver cirrhosis (n = 245), chronic hepatitis (n = 69) or non-cirrhotic portal hypertension (n = 2) arterial oxygen saturation (SaO2) was determined using a pulse oximeter. In patients with SaO2 < or = 92% in supine position and/or a decrease of > or = 4% after change from supine to upright position further diagnostic procedures were performed, including contrast-enhanced echocardiography and perfusion lung scan. RESULTS: Seventeen patients (5.4%) had a pathological SaO2. Four patients (1.3%) had HPS. HPS patients had a significant lower mean SaO2 in supine (89.7%, SD 5.4 vs. 96.0%, SD 2.3; p = 0.003) and upright position (84.3%, SD 5.0 vs. 96.0%, SD 2.4; p = 0.001) and had a lower mean PaO2 (56.2 mm Hg, SD 15.2 vs. 71.2 mm Hg, SD 20.2; p = 0.02) as compared to patients without HPS. The mean deltaSaO2 (difference between supine and upright position) was 5.50 (SD 7) in HPS patients compared to non-HPS patients who showed no change (p = 0.001). There was a strong correlation between shunt volume and the SaO2 values (R = -0.94). CONCLUSION: Arterial SaO2 determination in supine and upright position is a useful non-invasive screening test for HPS and correlates well with the intrapulmonary shunt volume.

Adult↗
PubMed2006

Effect of human presence and handling on circulating corticosterone levels in breeding blue tits (Parus caeruleus).

Birds may react to the presence of humans with an immediate primary behavioural reaction and with physiological responses, such as the activation of the hypothalamo-pituitary-adrenal axis. This study investigates the suite of behavioural and adrenocortical responses to the presence of humans and to handling in two subspecies of blue tits Parus caeruleus, a small hole-nesting passerine, during the period of feeding their nestlings. The first aim was to investigate whether the presence of humans near their nests elicits an adrenocortical response and whether the increase in circulating corticosterone is correlated with the behavioural reaction of the birds. The second aim was to determine the time-lag between the onset of capture and handling stress and the increase in circulating corticosterone levels. The third aim was to try to explain individual variation in the adrenocortical response to handling with 9 intrinsic and extrinsic factors (sex, age, body size, measures of body condition, time of day, and date). One half of the parents showed a behavioural reaction to our presence near the nest, such as alarming, and hesitating to enter the nestbox. However, the degree of behavioural reaction before handling was not related to circulating corticosterone levels which remained low. The results confirm that primary behavioural and adrenocortical reactions to the presence of predators are independent of each other. A comparison with published findings supports the hypothesis that birds react to predators with an adrenocortical response only in a situation that is imminently life-threatening. Hence, the primary behavioural response of the bird to a predator may determine whether or not an adrenocortical response is elicited. An adrenocortical response to handling started 3 min after capture in the nest box. Individual variation in baseline corticosterone levels could be explained by subspecies and body condition (fat stores), variation in handling-induced corticosterone levels by subspecies, body condition, body size, and time of day.

Adrenal Cortex Hormones↗
PubMed2005

Rapid loss of structural motifs in the manganese complex of oxygenic photosynthesis by X-ray irradiation at 10-300 K.

Structural changes upon photoreduction caused by x-ray irradiation of the water-oxidizing tetramanganese complex of photosystem II were investigated by x-ray absorption spectroscopy at the manganese K-edge. Photoreduction was directly proportional to the x-ray dose. It was faster in the higher oxidized S2 state than in S1; seemingly the oxidizing potential of the metal site governs the rate. X-ray irradiation of the S1 state at 15 K initially caused single-electron reduction to S0* accompanied by the conversion of one di-mu-oxo bridge between manganese atoms, previously separated by approximately 2.7 A, to a mono-mu-oxo motif. Thereafter, manganese photoreduction was 100 times slower, and the biphasic increase in its rate between 10 and 300 K with a breakpoint at approximately 200 K suggests that protein dynamics is rate-limiting the radical chemistry. For photoreduction at similar x-ray doses as applied in protein crystallography, halfway to the final Mn(II)4 state the complete loss of inter-manganese distances <3 A was observed, even at 10 K, because of the destruction of mu-oxo bridges between manganese ions. These results put into question some structural attributions from recent protein crystallography data on photosystem II. It is proposed to employ controlled x-ray photoreduction in metalloprotein research for: (i) population of distinct reduced states, (ii) estimating the redox potential of buried metal centers, and (iii) research on protein dynamics.

Amino Acid Motifs↗
PubMed2005

Characterisation of acyltransferases from Synechocystis sp. PCC6803.

As phylogenetic ancestors of plant chloroplasts cyanobacteria resemble plastids with respect to lipid and fatty acid composition. These membrane lipids show the typical prokaryotic fatty acid pattern in which the sn-2 position is exclusively esterified by C(16) acyl groups. In the course of de novo glycerolipid biosynthesis this prokaryotic fatty acid pattern is established by the sequential acylation of glycerol-3-phosphate with acyl-ACPs by the activity of different acyltransferases. In silico approaches allowed the identification of putative Synechocystis acyltransferases involved in glycerolipid metabolism. Functional expression studies in Escherichia coli showed that sll1848 codes for a lysophosphatidic acid acyltransferase with a high specificity for 16:0-ACP, whereas slr2060 encodes a lysophospholipid acyltransferase, with a broad acyl-ACP specificity but a strong preference for lysophosphatidyglycerol especially its sn-2 acyl isomer as acyl-acceptor. The generation and analysis of the corresponding Synechocystis knockout mutants revealed that lysophosphatidic acid acyltransferase unlike the lysophospholipid acyltransferase is essential for the vital functions of the cells.

Acyltransferases↗
PubMed2005

p38 MAP-kinase in cultured adult rat ventricular cardiomyocytes: expression and involvement in hypertrophic signalling.

Both alpha-adrenoceptor- and beta-adrenoceptor-stimulation lead to hypertrophic growth of the myocardium. But only beta-adrenoceptor-stimulation requires the pre-cultivation of cells with active TGF-beta. In order to define signalling molecules that are specifically involved in beta-adrenoceptor-dependent hypertrophy, changes in expression and hypertrophic responsiveness during pre-cultivation with TGF-beta were investigated. Isolated adult ventricular cardiomyocytes from rats were either cultured in 20% (v/v) foetal calf serum (FCS) to activate autocrine released TGF-beta or used without pre-treatment. Protein synthesis was analysed by (14)C-phenylalanine incorporation. Expression of signalling molecules was determined by immunoblotting. During cultivation of cardiomyocytes with active TGF-beta only the expression of p38 MAP-kinase increased. Subsequent stimulation of beta-adrenoceptors induced protein synthesis in a p38 MAP-kinase-dependent way. However, stimulation of beta-adrenoceptors activated p38 MAP-kinase irrespective of pre-treatment with TGF-beta. In the absence of this cytokine, hyperosmolarity or reconstitution of mechanical activity increased protein synthesis via p38 MAP-kinase activation in freshly isolated cells. In conclusion, activation of p38 MAP-kinase is a newly identified necessary signalling step required for beta-adrenoceptor induced hypertrophic growth. Like activation of adenyl cyclase, activation of p38 MAP-kinase is up-stream of the TGF-beta-induced coupling to the regulation of protein synthesis. Reconstitution of mechanical activity mimics the co-activation required and induced by TGF-beta.

Animals↗
PubMed2005

An acyl-CoA dehydrogenase is involved in the formation of the Delta cis3 double bond in the acyl residue of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis.

The lipopeptide antibiotic friulimicin, produced by Actinoplanes friuliensis, is an effective drug against Gram-positive bacteria, such as methicillin-resistant Staphylococcus epidermidis and Staphylococcus aureus strains. Friulimicin consists of a cyclic peptide core of ten amino acids and an acyl residue linked to an exocyclic amino acid. The acyl residue is essential for antibiotic activity, varies in length from C13 to C15, and carries a characteristic double bond at position Delta cis3. Sequencing of a DNA fragment adjacent to a previously described fragment encoding some of the friulimicin biosynthetic genes revealed several genes whose gene products resemble enzymes of lipid metabolism. One of these genes, lipB, encodes an acyl-CoA dehydrogenase homologue. To elucidate the function of the LipB protein, a lipB insertion mutant was generated and the friulimicin derivative (FR242) produced by the mutant was purified. FR242 had antibiotic activity lower than friulimicin in a bioassay. Gas chromatography showed that the acyl residue of wild-type friulimicin contains a double bond, whereas a saturated bond was present in FR242. These results were confirmed by the heterologous expression of lipB in Streptomyces lividans T7, which led to the production of unsaturated fatty acids not found in the S. lividans T7 parent strain. These results indicate that the acyl-CoA dehydrogenase LipB is involved in the introduction of the unusual Delta cis3 double bond into the acyl residue of friulimicin.

Acyl-CoA Dehydrogenase↗
PubMed2004

A novel BioXAS technique with sub-millisecond time resolution to track oxidation state and structural changes at biological metal centers.

Oxidation-state and structural changes at the metal center are crucial for the catalytic reactions of most metalloenzymes. The characterization of reaction intermediates is a prerequisite for understanding the catalytic mechanism. Frequently, intermediates are formed on the microsecond to millisecond timescale. To follow these reactions in real time represents a major challenge in structural biology. Time-resolved BioXAS is a particularly promising tool for resolving such intermediates. A novel approach for BioXAS, termed 'sampling-XAS', is presented. First room-temperature sampling-XAS results have been obtained for the manganese complex of oxygenic photosynthesis. Oxidation-state changes are monitored with a time resolution as good as 200 micros. The current prospects and limitations as well as future perspectives of time-resolved BioXAS are discussed.

Catalysis↗
PubMed2004

Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate the effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with that of cortisol, and compare aldosterone concentrations of healthy dogs with those of dogs with PDH. ANIMALS: 17 dogs with PDH and 12 healthy dogs. PROCEDURE: For dogs with PDH, the initial dose of trilostane was selected in accordance with body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12 weeks after initiation of treatment. Healthy dogs were evaluated only once. RESULTS: Serum aldosterone concentrations before ACTH stimulation did not change significantly after initiation of treatment with trilostane. At each evaluation after initiation of treatment, serum aldosterone concentrations after ACTH stimulation were significantly lower than corresponding concentrations before initiation of treatment. The overall effect of trilostane on serum aldosterone concentration was less pronounced than the effect on serum cortisol concentration. Median potassium concentrations increased slightly after initiation of treatment with trilostane. Dogs with PDH had significantly higher serum aldo sterone concentrations before and after ACTH stimulation than healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with trilostane resulted in a reduction in serum cortisol and aldosterone concentrations in dogs with PDH, although the decrease for serum aldosterone concentration was smaller than that for serum cortisol concentration. There was no correlation between serum concentrations of aldosterone and potassium during treatment.

Adrenocortical Hyperfunction↗
PubMed2002

First steps towards time-resolved BioXAS at room temperature: state transitions of the manganese complex of oxygenic photosynthesis.

Structural changes and redox transitions at the metal atoms of the active site are essential for the understanding of the catalytic mechanisms of biological metalloenzymes. First steps towards studying these processes by time-resolved X-ray absorption spectroscopy on protein samples (BioXAS) are reported. Photosystem II (PSII) catalyses the light-driven oxidation of bound water molecules at a tetranuclear manganese complex yielding the molecular oxygen of the atmosphere. In this work, first time-resolved XAS results under quasi-physiological conditions (at room temperature, non-crystalline samples) on PSII are presented. Perspectives of time-resolved BioXAS are discussed.

Lasers↗
PubMed2002

High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS with associated axonal loss. There is strong evidence for an autoimmune pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss. This underscores the potential role of MOG in MS pathogenesis. We performed a T cell reactivity pattern analysis of MS patients at the onset of relapse or progression of neurological deficits and controls that were stratified for the genetic risk factor HLA-DRB1*1501. For the first time, we show that there is an HLA-DR-restricted promiscuous dominant epitope for CD4(+) T cells within the transmembrane/intracellular part of MOG comprising aa 146-154 (FLCLQYRLR). Surprisingly, controls had broader T cell reactivity patterns toward MOG peptides compared with MS patients, and the transmembrane and intracellular parts of MOG were much more immunogenic compared with the extracellular part. Measurements of in vitro binding affinities revealed that HLA-DRB1*1501 molecules bound MOG 146-154 with intermediate and HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146-154 was comparable or better than myelin basic protein 85-99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients. This is the first study in which the data underscore the need to investigate the pathogenic or regulatory role of the transmembrane and intracellular part of MOG for MS in more detail.

Adult↗
PubMed2002

Ion suppression effects in liquid chromatography-electrospray-ionisation transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries.

Ion suppression effects during electrospray-ionsation mass spectrometry (ESI-MS) caused by different sample preparation procedures for serum were investigated. This topic is of importance for systematic toxicological analysis for which LC-ESI-MS has been developed with transport-region collision-induced dissociation (ECI-CID) and mass spectra library searching. With continuous postcolumn infusion of two test compounds-codeine and glafenine-the ion suppression effects of extracted biological matrix obtained after a standard liquid-liquid extraction, a mixed-mode solid-phase extraction (SPE) method, a protein precipitation method and a combination of precipitation with polymer-based mixed-mode SPE have been investigated. Extracted ion chromatograms of codeine ([M+H](+), m/z 300) and glafenine ([M-H](-), m/z 371) were used for monitoring ion suppression. Severe ion suppression effects for codeine and glafenine were detected in positive and in negative ionisation modes, respectively, in the LC-front peak after serum clean-up with SPE (acid/neutral fraction) and protein precipitation as well as with protein precipitation combined with SPE. Less ion suppression of codeine in positive mode was found with liquid-liquid extraction of serum samples. No ion suppression was detected with the second fraction of the mixed-mode SPE (using RP-C(8) and cation-exchange phase) in both ionisation modes. All suppression effects were caused by polar and unretained matrix components, which were present after extraction and/or protein precipitation. However, no specific ion suppression was seen after elution of the polar LC-front throughout the whole gradient. It could be demonstrated, that ion suppression is not generally present at any retention time when using reversed-phase HPLC with rather long gradient programs, but may play an important role in case of high-throughput LC-MS analysis, when the analyte is not separated from the LC-front, or in flow injection analysis without chromatographic separation.

Chromatography, Liquid↗
PubMedDate not supplied

LC-MS-MS analysis of the neuroleptics clozapine, flupentixol, haloperidol, penfluridol, thioridazine, and zuclopenthixol in hair obtained from psychiatric patients.

Hair samples of psychiatric patients were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) for the neuroleptics clozapine, flupentixol, haloperidol, penfluridol, thioridazine, and zuclopenthixol. In the study, these neuroleptics were administered to the patients regularly for a minimum of six months. Sample preparation was performed by washing, powdering with a ball mill, extraction of drugs from hair by ultrasonication with methanol, cleanup by solid-phase extraction and subsequent LC-MS-MS analysis using multiple reaction monitoring (MRM). Calibration was performed for all drugs in the range of 0.05 to 10 ng/mg using spiked hair powder and doxepin-d3 as internal standard. Twenty to 50 mg of hair powder was used and the detection limits of LC-MS-MS were below 0.05 ng/mg for all drugs tested. Therapeutic dosage, number of subjects, hair color, and detected amounts of drugs were as follows: clozapine (150400 mg/day; n = 3, light brown, medium brown, black; 0.47-0.92 ng/mg), haloperidol (150 mg/3 weeks; n = 1, black/gray; 12.2 ng/mg), penfluridol (20-30 mg/week; n = 2, medium brown, black; 0.08 ng/mg; not detected in one case), thioridazine (100-400 mg/day; n = 4, light brown, medium brown, black; 0.33-9.91 ng/mg, not detected in one case). Besides the active drugs also the desmethyl-metabolites of clozapine and thioridazine were detected by LC-MS-MS. However, flupentixol (5 mg/day; light brown hair) and zuclopenthixol (350 mg/3 weeks; light brown hair) were not detected by these methods in one case each, although the drugs were administered regularly to these patients. The comparison of dosage and hair color in two cases with thioridazine and penfluridol suggests that other interindividual factors may have an influence on drug concentration in hair.

Antipsychotic Agents↗