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D Müller

Publications and source records attributed to D Müller.

At least 73 records · Page 4Linked to original sources
PubMed2001

Corpus callosum and P300 in schizophrenia.

Functional abnormalities in the interhemispheric transfer via the corpus callosum in schizophrenia may result in filtering problems and information processing problems, which may in turn be related to the synchronization of cortical event-related activity. To explore whether a relationship exists between corpus callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late auditory event-related P300 potentials, 50 patients with schizophrenia as well as 50 healthy controls were examined. The absolute CC size and subregional areas, as well as the CC areas adjusted for total brain volume, were not significantly different between patients with schizophrenia and controls. While no significant group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies, P3a- and PSW-latencies were significantly prolonged for patients with schizophrenia. Absolute CC total size was significantly correlated with P3b-amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia, significant correlations were observed between the subregion of the posterior body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW-latencies were not significantly correlated to CC size in either patients with schizophrenia or healthy controls. The results are discussed in terms of the possibility that abnormalities in interhemispheric transfer may underlie the mechanisms of schizophrenia.

Adult↗
PubMed2001

Morphology and cytochrome P450 isoforms expression in precision-cut rat liver slices.

Precision-cut liver slices are a widely accepted in vitro system for the examination of drug metabolism, enzyme induction, or hepatotoxic effects of xenobiotics. The maintenance of the distinct lobular expression and induction pattern of phase I biotransformation enzymes, however, has not been examined systematically so far. Thus, in the present study, both longitudinal and transversal sections of male rat liver slices were investigated morphologically, as well as immunohistochemically for the expression of different cytochrome P450 (CYP) isoforms after prolonged incubation or after exposure to typical inducers. Histopathological examinations revealed an increasing vacuolization of the periportal hepatocytes mainly in the middle of the slices from 6 h of incubation on, paralleled by a loss of glycogen in the respective cells. After 24 h, mainly in the center of the slices, necroses of cells occurred. After 48 h of incubation, typically a central band of coagulative necrosis flanked by superficial layers of viable cells was observed. Freshly prepared slices displayed a CYP subtypes expression as normal liver specimen, a very low centrilobular CYP 1A1 immunostaining, but a strong CYP 2B1 and 3A2 expression predominantly in the central and intermediate lobular zones. From 2 h on, the immunostaining for CYP 2B1 and 3A2 was to some extent reduced. After 24 h of incubation with beta-naphthoflavone, the CYP 1A1 and 2B1 expression was induced mainly in the viable cells around central veins, around some portal fields with bigger vessels and in the cell layers close to the slice surface. At the same sites, phenobarbital led to an increased CYP 2B1 and 3A2 expression and dexamethasone to an elevated CYP 3A2 immunostaining. These results show, that an in vitro induction of phase I enzymes in precision-cut liver slices can be demonstrated also immunohistochemically.

Animals↗
PubMed2001

Monooxygenation, conjugation and other functions in cryopreserved rat liver slices until 24 h after thawing.

For the extensive use of precision-cut liver slices (particularly of human origin) for toxicological investigations successful cryopreservation is necessary. But so far, survival of thawed slices was limited to few hours. This was now overcome by modification of previous procedures. The concentration of DMSO as a cryoprotectant was enhanced to 30%, and washing steps after rapid thawing were omitted. The slices were frozen in liquid nitrogen, thawed at 38 degrees C and incubated immediately in Williams medium E. Protein and potassium contents were stable until 24 h. Glutathione content, amounting to nearly 50% of fresh slices, increased during incubation. High initial lactate dehydrogenase leakage dropped after medium change to less than half during 2-24 h. Testosterone hydroxylation and 7-ethoxycoumarin O-deethylation rates were similar to fresh slices, the latter reaction was inducible by beta-naphthoflavone within 24 h. Methylumbelliferone glucuronidation and p-nitrophenol glucuronidation and sulfation were well measurable and either maintained or decreased by about 50% until 24 h.Altogether, the results are encouraging for further experiments to standardise cryopreservation conditions and to investigate the suitability of this cryopreservation protocol with human liver slices.

Animals↗
PubMed2001

A conceptual framework for the study of the quality of rehabilitation.

PURPOSE: To propose a framework for the assessment and ongoing, continuous improvement of the quality of rehabilitation care. METHOD: The generally clarified and accepted approaches to the study of the quality of care are examined in view of the inherent characteristics of medical rehabilitation, and the differences between it and other fields of medical practice. RESULT: Process and outcome of care are distinct but complementary, and their elements should, in rehabilitation. be used jointly and simultaneously as indicators of quality. CONCLUSION: Rehabilitation is of long duration and consists of various phases, each of them focusing on a different issue. It is proposed to monitor activities of rehabilitation professionals (process elements) and constitute the focus of care of a given phase, and simultaneously to monitor relevant outcome elements attributable to the activities of the given phase. Comparison of monitored elements (the observed care) to their standards (the expected care) would enable assessment of the quality and its continuous improvement.

Humans↗
PubMed2001

[Endosonography in epithelial rectal tumors. Value of a differentiated therapy concept].

INTRODUCTION: Endorectal ultrasound (EU) is the most important examination for pretherapeutic stratification of primary rectal tumors. Preoperative histology and endosonography determine the therapeutic strategy by using the criteria of depth of infiltration (uT) and lymph node status (uN). METHODS: The effectiveness of endoluminal ultrasound in the preoperative differentiation between locally restricted tumors (adenomas and "low-risk" carcinomas, uT0/1, G1-2) and advanced rectal carcinomas (uT3) was assessed in a retrospective study of 284 patients. In the examination period (UZ) from 3/94 to 12/97 (UZ I) 104 patients (group 1) were examined with a 7-MHz endoprobe, and from 1/98 to 12/99 (UZ II), 116 (group 2) with a 10-MHz endoprobe. Additionally, in 64 patients (group 3) with an advanced uT3/4 or uN + tumor we compared the accuracy of ultrasound with computed tomography (CT). In this group 32 patients were restaged by EU and CT after preoperative chemoradiation. The results of präoperative endorectal ultrasound were correlated with the postoperative histological data. RESULTS: Concerning the whole period (UZ I and II) we achieved a total hit rate of 83.6% for adenomas and "low-risk" carcinomas (uT0/1, G1/2) by EU (79.8% in UZ I, 87.1% in UZ II). For advanced rectal carcinoma (> or = uT3) we found a total accuracy of 87.3% (82.7% in UZ I, 91.4% in UZ II). In 62 cases endosonographic lymph node status was correlated with postoperative histology during UZ II, with a hit rate of 64.5%. In group 3 (n = 64), in 32 patients without preoperative chemoradiation we found an accuracy for depth infiltration of 93% (EU) and 82% (CT). Concerning lymph node status there was a correlation of 57% (EU) and 64% (CT). After preoperative chemoradiation (n = 32) we found an accuracy of 91% (EU) and 73% (CT) for depth infiltration--for lymph node status 70% (EU) and 82% (CT). CONCLUSIONS: High accuracy in endoluminal ultrasound leads to a secure and differentiated stratification of therapy in primary rectal tumors. The hit rate concerning depth of infiltration is higher for EU than for CT both before and after chemoradiation, but not regarding lymph node status.

Adenoma↗
PubMed2001

[Effects of new cognitive-behavioral therapy programs for improvement of specific social skills of schizophrenics--a controlled study].

Based on the Integrated Psychological Therapy (IPT) for schizophrenia patients, the Berne group developed three specific cognitive behaviour therapy programmes for treating residential, vocational, and recreational functioning. We added new cognitive-emotional methods to these programmes that were devised especially for schizophrenia patients, taking into consideration the criticism of traditional social skill training methods. In the present multicentre study, these new programmes (experimental group) were compared with a traditional social skills training programme (control group, IPT "Social Skills" subprogramme). Both the therapy and aftercare phase each lasted 12 weeks and the follow-up phase 1 year. Assessment instruments covered psychopathology, cognitive functioning, and social adjustment. Higher ratings of global treatment effects and significant reductions in symptoms were obtained in the experimental group. In view of the favourable results, these newly designed social skill training programmes may replace more conventional therapy approaches in the future.

Adult↗
PubMed2001

Single-cell RT-PCR analysis of N-methyl-D-aspartate receptor subunit expression in rat locus coeruleus neurones.

Whole-cell patch-clamp recordings were performed on 12- to 15-day-old rat locus coeruleus neurones in a midpontine slice preparation. Application of noradrenaline (100 microM) and N-methyl-D-aspartate (NMDA; 100 microM) induced a small outward current and a distinct inward current, respectively. Single-cell reverse transcriptase-polymerase chain reaction (scRT-PCR), used to analyse the expression pattern of NMDA receptor subunits 2A, 2B, and 2C (NR2A-C) subsequent to electrophysiological characterization, demonstrated differences in the capacity of individual locus coeruleus neurones to express NR2A-C mRNA. NR2C mRNA expression predominated over those of NR2A and NR2B mRNA in most neurones. In addition, in neurones containing NR2C mRNA NMDA induced significantly larger currents than in cells lacking expression of this gene. RT-PCR studies performed on tissue preparations of adult rats also revealed a distinct expression of NR2C mRNA. In conclusion, the present data demonstrate differences in the mRNA expression pattern of NR2A-C of individual locus coeruleus neurones with a predominant NR2C mRNA expression in the majority of the cells.

Animals↗
PubMed2001

Transgenic mice with neuronal overexpression of bcl-2 gene present navigation disabilities in a water task.

In the CNS, Bcl-2 is an antiapoptotic gene involved in the regulation of neuronal death. Transgenic mice overexpressing the human gene Bcl-2 (Hu-bcl-2 mice) showed delayed acquisition in two tasks requiring them to find a hidden platform starting from either a random or a constant starting location. The same mice were not deficient in another task requiring them to find a visible platform suggesting that the delay observed was not due to motor, visual or motivational deficits in the water. The delay observed in Hu-bcl-2 mice was more important in the random starting test in which the allocentric demand for navigation was stronger. The results suggested that allocentric navigation is particularly sensitive to abnormal CNS maturation following the overexpression of the bcl-2 gene. The specific deficits (motor learning, fear-related behavior and allocentric navigation) observed in Hu-bcl-2 mice suggest that the regulation of developmental neuronal death is crucial for multisensorial learning and emotional behavior.

Animals↗
PubMed2001

Modulating angiotensin II-induced inflammation by HMG Co-A reductase inhibition.

Angiotensin (Ang) II is capable of producing inflammatory changes by signals through its AT1 receptor. Reactive oxygen species production, adhesion molecule expression, chemokines, and other mediators are involved. Nuclear factor-kappaB (NK-kappaB) and activator protein 1 (AP-1) are two of the transcription factors activating the responsible genes. We have studied Ang II-independent modulating effects in a double transgenic rat model harboring the human renin and angiotensinogen genes. We have recently focused on the protective effects of HMG-CoA reductase inhibition and review these data here. We found that cerivastatin decreased mortality, lowered blood pressure, preserved renal function, decreased cardiac hypertrophy, and inhibited the entire chain of inflammatory events. Furthermore, NF-kappaB and AP-1 activation was sharply attenuated. We also observed that cerivastatin blocked ERK1/2 phosphorylation in vivo and in vitro. Cerivastatin also inhibited phorbol ester-transmitted events in vascular smooth muscle cells. Because Rho, a member of the Ras protein superfamily is important to Ang II-dependent and -independent vascular smooth muscle signaling events, we suggest that cerivastatin may act by inhibiting the prenylation, membrane anchoring, and subsequent activation of Ras proteins. These data may in part explain cholesterol-independent, HMG-CoA reductase-related, protective effects.

Angiotensin II↗
PubMed2001

Cytochrome P450 (P450) isoforms expression, P450 concentration, monooxygenase activities, reactive oxygen species formation, lipid peroxidation, and glutathione content in wild catch carp and tench liver--influence of a two weeks exposure to phenobarbital.

Carps, both sexes, 3 years old, weighing about 1 kg, and tenches of both sexes, 6 years old, weight about 250 g, were caught from a Thuringian lake without industrial pollution in November 1995 (fish without food uptake, water temperature at about 10 degrees C) and kept for 2 weeks in basins with clean water and addition of 0, 0.1, 1.0 or 10.0 mg/l phenobarbital-Na (PB). The concentration of PB was controlled during and at the end of the exposure period. The animals were fed pellets, but no food uptake was observed. After 24-48 h in fresh water the fish were sacrificed and the following hepatic parameters were immediately determined biochemically: monooxygenase functions: cytochrome P450 (P450) content, ethylmorphine N-demethylation (EN), ethoxycoumarin O-deethylation (ECOD), ethoxyresorufin O-deethylation (EROD), 7-benzyloxy-4-methyl-coumarin O-debenzylation (BCDB); oxidase function indicators: microsomal Fe2+/NADPH dependent hydrogen peroxide formation (H2O2), microsomal Fe2+/NADPH dependent luminol and lucigenin amplified chemiluminescence (LMCL, LCCL), microsomal Fe2+/NADPH dependent lipid peroxide formation (LPO); oxidative state: lipid peroxidation products (TBARS) and GSH and GSSG. Additionally, the expression of three P450 isoforms, 1A1, 2B and 3A, was assessed immunohistochemically in tissue samples from brain, gill, heart, spleen, liver, gut and ovary of both fish species and in kidney of tenches. PB did not influence body or liver weights, but increased liver P450 concentration in both species by 50-100%, though not significantly. Carp: PB increased both EN and EROD significantly, but not ECOD and BCDB; H2O2 and TBARS were enhanced significantly. LPO, LMCL and LCCL were not significantly influenced. Tench: PB increased all monooxygenase reactions (EN, ECOD, BCDB and EROD), though only significantly ECOD; H2O2 was elevated only after treatment with 0.1 mg/l PB, whereas LPO was decreased (!) after treatment by all three concentrations, though significantly only after 1.0 mg/l PB. LMCL was depressed (not significantly), but LCCL increased 5fold. TBARS were significantly enhanced. P450 1A1 subtype expression was concentration dependently elevated by PB in gill and liver of both fish and in the heart and kidney of tenches, P450 2B and 3A isoforms expression was induced in brain, gill, heart, liver and gut of both fish and in the kidney of tenches. In summary, the increased activities of the monooxygenase reactions tested and the elevated expression of all three P450 isoforms investigated in certain tissues indicate an induction of the P450 families 1, 2 and 3 by PB in fish.

Animals↗
PubMed2001

The effect of the skull on event-related P300.

OBJECTIVES: Event-related potentials (EP) indicate neuronal processes with a high temporal resolution, while functional magnetic resonance imaging (fMRI) has a high spatial distribution. Information from both techniques may complement each other. However, this combination is fraught with difficulty because of a possible interference of the skull or the scalp with scalp-recorded EP. The aim of the present study was to investigate this influence of skull and scalp thicknesses on event-related P300 potentials. METHODS: Thirty healthy controls were examined using an auditory evoked P300 elicited by a standard oddball paradigm. Skull and scalp thicknesses were determined using coronal T2-weighted magnetic resonance imaging (MRI). RESULTS: P3b-amplitudes were significantly correlated with temporo-parietal skull thickness (r=-0.42; P=0.021; regression slope of -1.14 microV/mm skull thickness), whereas scalp had no influence on P300. The amplitude of the more frontal subcomponent P3a was not related to frontal skull thickness. CONCLUSIONS: Therefore, the utility of P300 as a research tool can be enhanced when adjustment for skull thickness is made.

Adult↗
PubMed2001

Thrombolytic therapy in children--clinical experiences with recombinant tissue-plasminogen activator.

For the improvement of thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA) in children, more clinical data are needed. We retrospectively analyzed the clinical course of 20 patients (age ranging from 1 day to 16 years) with venous thrombosis (n = 16), arterial thrombosis (n = 2), and purpura fulminans by meningococcosis (n = 2). The venous thromboses were localized in the iliac-femoral veins (n = 9), brachiocephalic-jugular-subclavian veins (n = 6), and the superior caval vein (n = 1). The arterial occlusions were localized in the abdominal aorta and in the left pulmonary artery. Central venous catheters were of pathogenetic importance in seven cases. The patients were treated with rt-PA for 3 hours to 13 days. The dose ranged between 0.2 and 0.5 mg/kg for the initial bolus and 1.0 to 2.0 mg/kg/d for the continuous infusion. Nineteen patients received simultaneously low-dose unfractionated heparin. Complete clot lysis was detected in 11 cases, a partial lysis in 1, and in 8 patients thrombolytic therapy was not successful. An episode of hematemesis in one patient represented the only serious side effect observed in our study. A systemic decrease in fibrinogen concentration was also rare. In conclusion, thrombolysis with rt-PA represents an effective and safe therapy for children at the dosage used.

Child↗
PubMed2001

Para-nitrophenol glucuronidation and sulfation in rat and human liver slices.

Para-nitrophenol (PNP) is a well-known substrate for both phase I (hydroxylation at cytochrome P450) and phase II reactions (glucuronidation and sulfation). HPLC separation of PNP conjugates has already been described, but not for respective studies with liver slices, which nowadays have proven to be a suitable model for metabolic studies. Therefore we adapted an HPLC method for the simultaneous measurement of PNP glucuronidation (PNP-G) and sulfation (PNP-S) in this in vitro system. Both activities are substantially maintained over an incubation period of 24 h. PNP-G activity, however, seems to be better preserved, as indicated by stable values for PNP-G but reduced PNP-S values after 48 h liver slice preincubation. 24 h exposure of the slices to beta-naphthoflavone or phenobarbital does not change PNP-G or PNP-S activities.

Animals↗
PubMed2001

Advanced breast biopsy instrumentation for the evaluation of impalpable lesions: a reliable diagnostic tool with little therapeutic potential.

OBJECTIVE: To assess the potential of advanced breast biopsy instrumentation (ABBI) to clarify the diagnosis of impalpable mammographic lesions and to remove the entire malignant lesions with clear margins. DESIGN: Prospective assessment in a consecutive series of patients. SETTING: University hospital, Basel, Switzerland. SUBJECTS: 139 patients presenting with 144 impalpable microcalcifications or solid nodular densities evident on screening and follow-up mammograms that were suspicious of malignancy. MAIN OUTCOME MEASURES: Feasibility, sensitivity, efficiency in obtaining definitive diagnoses in an outpatient clinic under local anaesthesia, feasibility of complete removal of a primary malignancy, and intervention-related morbidity. RESULTS: The ABBI procedure was successful in 135/144 (94%); an accurate diagnosis was made in 129/130 patients followed up (99%), sensitivity for malignant lesions was 31/32 (97%) and there were 2 complications (2%). Margins of the biopsy cylinder contained a malignant lesion in 26/31 (84%). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low morbidity. As in other published series margins were often not clear of tumour and therefore the therapeutic use of the ABBI procedure is limited.

Adult↗
PubMed2001

Cross-cultural adaptation of the Minnesota Living with Heart Failure Questionnaire for German-speaking patients.

We performed a cross-cultural adaptation of the "Minnesota Living with Heart Failure Questionnaire" (LHFQ) for use in German-speaking chronic heart failure patients. The instrument was translated and back translated, pre-tested and reviewed by a committee. The German version was tested in 114 patients with chronic heart failure. Reliability was assessed by a test-retest procedure and Cronbach's coefficient alpha of internal consistency (0.94). To assess concurrent validity, we compared the LHFQ sum scores with the New York Heart Association classification rating (r = 0.53; p < 0.0001), the 6-minute walk (r = -0.39; p < 0.0001), the left ventricular ejection fraction (r = -0.24; p = 0.011) and big-endothelin (r = 0.27; p = 0.004). Construct validity on the LHFQ scores in comparison with the Medical Outcomes Study SF-36 Health Survey (MOS SF-36) was significant (-0.41 to -0.74; all p < 0.0001). The reliability and validity of the German version of the LHFQ was proved; the questionnaire can be recommended for use in future clinical trials.

Aged↗
PubMed2001

Phosphorylation disrupts the central helix in Op18/stathmin and suppresses binding to tubulin.

Protein phosphorylation represents a ubiquitous control mechanism in living cells. The structural prerequisites and consequences of this important post-translational modification, however, are poorly understood. Oncoprotein 18/stathmin (Op18) is a globally disordered phosphoprotein that is involved in the regulation of the microtubule (MT) filament system. Here we document that phosphorylation of Ser63, which is located within a helix initiation site in Op18, disrupts the transiently formed amphipathic helix. The phosphoryl group reduces tubulin binding 10-fold and suppresses the MT polymerization inhibition activity of Op18's C-terminal domain. Op18 represents an example where phosphorylation occurs within a regular secondary structural element. Together, our findings have implications for the prediction of phosphorylation sites and give insights into the molecular behavior of a globally disordered protein.

Circular Dichroism↗
PubMed2001

Characterization of relaxin binding in the uterus of the marmoset monkey.

The ovarian peptide hormone relaxin (RLX) plays an important role in the regulation of the endometrium both during the cycle and in early pregnancy. RLX interacts with specific receptors on endometrial stromal cells causing these to decidualize. In order to characterize the molecules with which RLX interacts in the primate uterus, a methodology based on a fully bioactive preparation of biotinylated porcine RLX was applied to cryosections of the uterus of female marmoset monkeys. Specific RLX binding was weakly detected in the proliferative phase in isolated endometrial stromal cells. In the secretory phase, the positively reacting cells increased in staining intensity and in number and also included some epithelial cells. Further increases occurred in pregnancy, but RLX binding in the endometrium decreased at the end of the cycle if pregnancy did not occur. The myometrium showed weak staining which did not vary through the cycle, but increased in pregnancy. Electrophoretic analysis of the RLX-binding moieties in these tissue sections indicated that a protein of approximately 40 kDa was the principal RLX-binding molecule, while minor specific bands were detectable at approximately 100 and approximately 200 kDa. The binding of biotinylated RLX could be specifically suppressed by co-incubation with unlabelled RLX, but not by insulin, IGF-I or biotin. This technique therefore allows the detection and molecular characterization of specific RLX binding in the primate uterus. In the marmoset monkey, the pattern of specific binding closely reflects the RLX-dependent physiology during implantation and early pregnancy, implying the probable involvement of a specific RLX receptor.

Animals↗