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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 307 records · Page 17Linked to original sources
PubMed1996

Visual hallucinosis: the major clinical determinant of distorted chromatic contour perception in Parkinson's disease.

Recently distorted chromatic contour perception has been demonstrated in Parkinson's disease (PD). The aim of our study is to determine the clinical factors which influence chromatic contour perception in PD. Chromatic and achromatic contour perception, colour discrimination and clinical data were evaluated in 73 patients with PD. We used a computer-aided method to determine the chromatic fusion time (CFT) which indicates the acuity of monochromatic contour perception. Chromatic CFT was generally shortened in patients as compared to controls (p < 0.01), whereas achromatic CFT was not significantly different. Variance analysis revealed the ability of colour discrimination and the risk of visual hallucinations as statistically significant (p < 0.05) variables influencing contour perception of certain stimuli. In contrast, disease stage, disease duration and disease severity have no relevant effect on chromatic contour perception in Parkinson's disease. On the basis of those properties one may suggest that distorted chromatic contour perception is due to an impairment at a central stage of visual processing in PD and an imbalance of the serotonergic system. Whether CFT is a reliable method to predict the individual risk of hallucinosis in PD has to be evaluated.

Aged↗
PubMed1996

Sustained-release of levodopa: single dose study of a new formulation.

Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, cross-over double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations).

Aged↗
PubMed1996

The motor performance test series in Parkinson's disease is influenced by depression.

The Motor Performance Test Series (MPTS) is widely used for treatment control in Parkinson's disease (PD). To elucidate the possible influence of depression on the fine motor skills in PD, 54 patients with idiopathic PD were investigated with the MPTS. 27 patients with major intensity of depression were compared to 27 age and motor disability matched patients with minor symptoms of depression, evaluated by the Zung depression scale. As determined by the subtest aiming, a significant lower ability for precise, quick complex arm-hand movements in depressed Parkinsonian patients was found. This result may be explained partly by motivation deficits in depressed patients with PD. On the other hand impairment of special motor loops including frontal lobe projections to specific thalamic subnuclei or to the caudate nucleus may cause disturbances of the subtest aiming in depressed Parkinsonian patients. On the basis of these findings impaired aiming may be explained by diminished ability for complex, semivoluntary movements in depressive Parkinsonian patients. The influence of psychiatric comorbidity on MPTS subtest aiming has to be considered in further therapy studies using evaluation of motor deficits by MPTS.

Adult↗
PubMed1996

Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients.

Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, beta-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may easily be formed by cyclization of indoleamines with e.g. aldehydes. For further elucidation of the role of beta-carbolines in neurodegenerative disorders harman and norharman levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and compared to an age- and sex-matched control group (n = 14). CSF levels of norharman and harman in PD were significantly higher compared to controls. These results may suggest a possible role of harman and norharman or its N-methylated carbolinium ions in the pathophysiological processes initiating PD. However the origin of increased levels of these beta-carbolines remains unclear. On the one hand one may speculate, that unknown metabolic processes induce the increased synthesis of harman and norharman in PD. On the other hand a possible impact of exogenous sources may also be possible.

Adult↗
PubMed1996

Depression in Parkinson's disease: biogenic amines in CSF of "de novo" patients.

INTRODUCTION: Etiology of depression in Parkinson's disease (PD) is associated with serotonergic dysfunction. Previous studies, supporting this hypothesis, were performed on patients treated with antiparkinsonian drugs. To eliminate the influence of parkinsonian drug therapy and to elucidate significance of different biochemical pathways in PD associated with depression we determined levels of biogenic amines in cerebrospinal fluid (CSF) of 26 untreated "de novo" Parkinsonian patients. MATERIAL AND METHODS: Patients were scored with the Hamilton depression scale (HD) and subdivided into groups with HD score > or = 18 and HD score < 18. Diagnosis of depression was made according to DSM III R. Both groups were matched for age and motor disability. RESULTS: In both groups no significant differences appeared between CSF levels of dopamine, noradrenaline, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindole acetic acid, determined by high-performance liquid chromatography. DISCUSSION: In contrast to previous studies on treated Parkinsonian patients no sign of altered serotonin metabolism especially in context with severity of depression in early stages of PD was found. Due to our results, we suggest, that biochemical markers of depression in CSF of PD may be influenced by antiparkinsonian therapy and that depression in PD may respond to serotonin reuptake inhibitors mainly in later stages of PD.

Aged↗
PubMed1996

Subtypes of the type 4 cAMP phosphodiesterases: structure, regulation and selective inhibition.

The 'famille nombreuse' of cyclic nucleotide phosphodiesterases, responsible for degrading the ubiquitous second messenger molecules, cAMP and cGMP, maintains its place as a major focus of interest for many research laboratories in both academia and industry. The increase in knowledge of the primary sequences, plus the availability of selective inhibitors, are rapidly improving our insight into the structure, regulation and function of these pivotal enzymes of cellular homeostasis. Here, Thomas Müller, Peter Engels and John Fozard focus on family 4 of the phosphodiesterases, which is of particular interest owing to both the number of genes (and splice variants) and the emergence of selective inhibitors, which are enabling the functional significance of these enzymes to be defined.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Eclampsia after polychemotherapy for nodal-positive breast cancer during pregnancy.

We report the case of a 39-year-old para-4 gravida-4 who received polychemotherapy 5-fluorouracil 600 mg/m2, cyclophosphamide 600 mg/m2 and epirubicin 50 mg/m2 for invasive breast cancer (pT2N2Mo) with extensive metastatic involvement of all 23 axillary lymph nodes removed at 29 gestational weeks. Soon after the second course of chemotherapy at 35 weeks, she developed two eclamptic tonic-clonic seizures which were treated by antihypertensive and anticonvulsive drugs and delivery of a healthy infant, 1650 g (< 10th percentile) by cesarean section. That this patient indeed suffered from eclampsia was supported by the findings of transient postpartum severe hypertension (peak 170/110 mmHg), proteinuria (peak 3.2 g/24 h), incomplete features of the HELLP syndrome (thrombocytopenia 81,000/mm3, haptoglobin < 10 mg/dl) and of DIC, and by the results of cerebral CT scanning showing two 1-cm ischemic lesions. Since the detrimental effect of antineoplastic agents on the rapidly proliferating trophoblast is well known and as abnormal placental function, such as in triploidy, trisomy or hydatiform mole, has been associated with an increased risk for preeclampsia/eclampsia, a possible causal relationship between polychemotherapy and the subsequent development of this rare disorder is suggested.

Adult↗
PubMed1996

Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram.

The PDE2, cyclic GMP-stimulated, and the PDE4, cyclic AMP-specific enzymes provide the major, detectable cyclic AMP phosphodiesterase activities in murine thymocytes. In the absence of the cyclic GMP, PDE4 activity predominated (approximately 80% total) but in the presence of low (10 microM) cyclic GMP concentrations, PDE2 activity constituted the major PDE activity in thymocytes (approximately 80% total). The PDE4 selective inhibitor rolipram dose-dependently inhibited thymocyte PDE4 activity (IC50 approximately 65 nM). PDE2 was dose-dependently activated (EC50 approximately 1 microM) by cyclic GMP and inhibited by erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) (IC50 approximately 4 microM). EHNA was shown to serve as a selective inhibitor of PDE-2 activity as assessed from studies using separated PDE1, PDE2, PDE3 and PDE4 species from hepatocytes as well as human PDE2 and PDE4 enzymes. EHNA completely ablated the ability of cyclic GMP to activate PDE2 activity, whilst having a much smaller inhibitory effect on the unstimulated PDE2 activity. EHNA exhibited normal Michaelian kinetics of inhibition for the cyclic GMP-stimulated PDE2 activity with Hill plots near unity. Apparent negative co-operative effect were seen in the absence of cyclic GMP with Hill coefficients of approximately 0.3 for inhibition of PDE2 activity. Within 5 min of challenge of thymocytes with the lectin phytohaemagglutinin (PHA) there was a transient decrease (approximately 83%) in PDE-4 activity and in PDE2 activity (approximately 40%). Both anti-TCR antibodies also caused an initial reduction in the PDE4 activity which was followed by a sustained and profound increase in activity. In contrast to that observed with PHA, anti-TCR/CD3 antisera had little effect on PDE2 activity. It is suggested that, dependent upon the intracellular concentrations of cyclic GMP, thymocyte cyclic AMP metabolism can be expected to switch from being under the predominant control of PDE4 activity to that determined predominantly by PDE2 activity. These activities may be rapidly and differentially regulated following ligation of different cell surface receptors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Dielectric spectroscopy of single human erythrocytes at physiological ionic strength: dispersion of the cytoplasm.

Usually dielectrophoretic and electrorotation measurements are carried out at low ionic strength to reduce electrolysis and heat production. Such problems are minimized in microelectrode chambers. In a planar ultramicroelectrode chamber fabricated by semiconductor technology, we were able to measure the dielectric properties of human red blood cells in the frequency range from 2 kHz to 200 MHz up to physiological ion concentrations. At low ionic strength, red cells exhibit a typical electrorotation spectrum with an antifield rotation peak at low frequencies and a cofield rotation peak at higher ones. With increasing medium conductivity, both electrorotational peaks shift toward higher frequencies. The cofield peak becomes antifield for conductivities higher than 0.5 S/m. Because the polarizability of the external medium at these ionic strengths becomes similar to that of the cytoplasm, properties can be measured more sensitively. The critical dielectrophoretic frequencies were also determined. From our measurements, in the wide conductivity range from 2 mS/m to 1.5 S/m we propose a single-shell erythrocyte model. This pictures the cell as an oblate spheroid with a long semiaxis of 3.3 microns and an axial ratio of 1:2. Its membrane exhibits a capacitance of 0.997 x 10(-2) F/m2 and a specific conductance of 480 S/m2. The cytoplasmic parameters, a conductivity of 0.4 S/m at a dielectric constant of 212, disperse around 15 MHz to become 0.535 S/m and 50, respectively. We attribute this cytoplasmic dispersion to hemoglobin and cytoplasmic ion properties. In electrorotation measurements at about 60 MHz, an unexpectedly low rotation speed was observed. Around 180 MHz, the speed increased dramatically. By analysis of the electric chamber circuit properties, we were able to show that these effects are not due to cell polarization but are instead caused by a dramatic increase in the chamber field strength around 180 MHz. Although the chamber exhibits a resonance around 180 MHz, the harmonic content of the square-topped driving signals generates distortions of electrorotational spectra at far lower frequencies. Possible technological applications of chamber resonances are mentioned.

Biophysical Phenomena↗
PubMed1996

[Premature termination of pregnancy in the 2nd and 3rd trimester. Serial administration of 1 mg gemeprost vaginal suppositories versus intravenous sulproston].

Comparison of 1 mg Gemeprost-Vaginal Suppositories Serial Application versus Sulproston i.v.: Three different regimens for the termination of second and third trimester pregnancies by the use of prostaglandins (PG) were compared in a retrospective analysis. In group A (n = 16) terminations were attempted by continuous i.v. Infusion of Sulproston 9 hours after administration of a 3 mg-PGE2-vaginal tablet overnight. In group B (n = 22), i.v. Sulproston was started 2 hours after priming with 1 mg Gemeprost-vaginal suppositories. The outcome of these two regimens was compared with that of repeated administration of 1 mg Gemeprost-vaginal suppositories at 6-hourly intervals (group C, n = 25). In each group. If uterine contractions failed to appear after one day, the treatment was discontinued for a sleep rest over night and then resumed. Genetic disorders or fetal malformations were the most frequent reasons for termination. Patients with intrauterine fetal demise, rupture of the membranes, preterm labour or a ripe cervix (Bishop Score > 3) were excluded. Median time intervals from induction to abortion were 33 hours in group A and 23 hours in each Group B and C. The rate of fetal expulsions within 12, 24 and 36 hours in groups B and C were similar. Women of parity > or = 1 showed significantly shorter intervals than nulliparae in groups A and C. Only one woman (in group A) failed to expel after induction, in four other cases (in groups A and B) complications (local thrombophlebitis, bronchospasm) were noted. The serial administration of 1 mg Gemeprost-vaginal suppositories at 5-hourly intervals showed fewer side effects and seems to be as efficient as sulproston i.v. after cervical ripening.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Electron microscopic demonstration of intracelluar promethazine accumulation sites by a precipitation technique: application to the cerebellar cortex of the mouse.

A method is described that allows electron microscopic identification of the phenothiazine neuroleptic promethazine after supravital intracardiac injection of high drug concentrations (greater than or equal to 3 %). The cerebellar cortex of the mouse was used for the investigation. This procedure is based on simultaneous fixation of drug and tissue by immersion in a paraformaldehyde-glutaraldehyde solution with the addition of phosphomolybdic acid. The electron microscopic investigation revealed that the drug could easily be identified as an electron-dense precipitate. Subpopulations of neurons exhibited a higher affinity for the drug than others, but no preference for any nerve cell type was detected. Closer study showed that promethazine accumulated primarily within the cytoplasm, where it was bound to the endoplasmic reticulum. Furthermore, promethazine storage was observed within mitochondria and vesicular structures. Drug binding was also seen in the regions of synapses but without any predilection for these structures. Because this precipitation technique also appears to be well-suited for the ultrastructural identification of other drugs, it offers multiple possibilities for application.

Animals↗
PubMed1996

Heterologous expression and characterisation of mouse brain fatty acid binding protein.

A novel brain-type member of the fatty acid binding protein family (B-FABP) was heterologously expressed in Escherichia coli, either as inclusion bodies at 37 degrees C or in soluble form at 22 degrees C. Both B-FABP renatured from inclusion bodies and the solubly expressed protein could be purified to homogeneity by anion exchange chromatography and gel filtration in a functional conformation as they bound oleic acid with high affinity. None of the five cysteines of B-FABP was involved in disulphide bond formation. Isoelectric focusing revealed heterogeneity of the renatured protein but not of the solubly expressed protein. By Western blotting using affinity purified rabbit antibodies raised against the recombinant B-FABP it was demonstrated that in adult mice, B-FABP is predominantly expressed in the olfactory bulb.

Amino Acid Sequence↗
PubMed1996

The innervation of taste buds in the soft palate of the rat as revealed by methylene blue staining.

Light microscopic data on the innervation of taste buds in the soft palate of the rat obtained by methylene blue (MB) supravital staining are presented here for the first time. The taste pore including subpopulations of taste bud cells and nerve fibers were stained. Intragemmal nerve fibers were detected ascending up to the taste pore; this suggests the possibility of additional paracellular pathways in taste transduction directly via nerve fibers. Moreover, relatively large bulbous or laminar enlargements of the intragemmal nerve fibers were found. The branches of these nerve fibers, showing minute spiny protuberances, appeared to anastomose. Some perigemmal nerve fibers were also seen in close apposition to the taste pore. The basal plexus in the vicinity of the taste buds showed enlargements which resembled the Merkel's discs, but were significantly smaller. These structures did not occur in the subgemmal part of the basal plexus. Regarding the oxygen-dependency of the staining reaction, it was speculated that both MB and oxygen were attracted by iron-containing enzymes. Therefore, the strong affinities for MB shown by subpopulations of nerve fibers and taste bud cells were explained by their high requirements for oxygen. Furthermore due to its selectivity for intraepithelial nerve fibers and sensory cells, the method applied here is well-suited for routine use in light microscopy.

Animals↗
PubMed1996

Supravital uptake of methylene blue by dendritic cells within stratified squamous epithelia: a light and electron microscope study.

Electron microscopic data on methylene blue staining of dendritic cells in the epithelia of the soft palate and skin of the mouse after supravital dye injection are presented. The ultra-structural details were compared with corresponding light microscopic findings. Methylene blue stained tissue was fixed by immersion in a paraformaldehyde-glutaraldehyde solution containing phosphomolybdic acid. The ensuing dye precipitate was stabilized by ammonium heptamolybdate. The light microscopic investigation revealed that selective staining of dendritic cells depended on the presence of ambient oxygen. In addition, delicate morphological characteristics, like spinous structures of the dendrites, were visible. Some cells also showed terminal enlargements of the dendrites close to the surface of the epithelium. In general, visualization of morphological detail was superior to that obtained by conventional histological and immunohistochemical procedures. Nerve fibers were also stained within the epithelium as well as the subepithelial connective tissue. At the electron microscopic level, the dye was clearly identified as an electron dense precipitate that accumulated primarily within the cytoplasm near the plasma membrane. Furthermore, it was bound to the chromatin of the nuclei. No significant staining of mitochondria or other organelles was seen. Within the cytoplasm, the oxygen-dependent binding sites may be associated with heme proteins that attract both the dye in its reduced lipophilic leuco form and oxygen, followed by generation of oxygen radicals and a reoxidation of the leuco form to the cationic blue dye. Because of its selectivity for intraepithelial dendritic cells, the method described here supplements immunocytochemical procedures at both the light and electron microscopic levels.

Animals↗
PubMed1996

Seroprevalence of orthopox virus specific antibodies in red foxes (Vulpes vulpes) in the Federal State Brandenburg, Germany.

The prevalence of orthopox virus (OPV)-specific antibodies in 1,040 red foxes (Vulpes vulpes) was evaluated on a large scale in the German Federal State Brandenburg. Serum samples were selected from 809 communities within the study area from January 1991 to September 1994 by simple random sampling. Screening was carried out by an indirect enzyme-linked immunosorbent assay (ELISA). Orthopox virus-specific antibodies were found in 162 (16%) of the 1,040 fox sera. Furthermore 154 (15%) sera were considered suspect positive. The specificity of the antibodies detected in ELISA-positive and suspect positive sera was confirmed by Western blotting. Presence of OPV-antibodies occurred in 291 communities. No correlation of OPV-antibodies findings to latitude or characteristic topographical and ecological peculiarities of the study area was found. Although the causative agent is still unknown we believe that orthopox viruses probably have a ubiquitous presence among red foxes.

Animals↗
PubMed1996

Analysis of adhesion molecules in myocardial biopsies of cardiac allografts and coronary artery disease with CABG.

Interactions of leukocytes with vascular endothelium are important components of inflammation tissue reactions and have been implicated in cardiac transplant rejection and demonstrated to be mediated by cell adhesion molecules (CAM's). The expression of ICAM-1, VCAM-1 and E-selectin in human myocardium is variable and little is known about the expression of LFA-1 and Mac-1 during allograft rejection. This study investigated these CAM's in myocardial biopsies of transplanted hearts (HTX) and of coronary artery disease eligible for coronary artery bypass grafting (CABG) as non-inflammatory controls and explicitly examines vascular endothelium, cardiomyocytes and infiltrating cells. Immunohistochemistry was performed using the APAAP-method and directing specific mouse anti-human monoclonal antibodies against ICAM-1 (CD54), VCAM-1 (CD106), E-selectin (CD62E), alpha-LFA-1 (CD11a), alpha-Mac-1 (CD11b), alpha-p150/95 (CD11c) and the beta2-integrin chain (CD18). CD18, LFA-1 (CD11a), Mac-1 (CD11b) and p150/95 (CD11c) were markedly expressed on infiltrating immunocytes in HTX compared to CABG where no expression of beta2-integrins was observed. Cardiac allografts demonstrated a strong expression of ICAM-1 on vascular endothelium and on infiltrating cells. ICAM-1 was not detected on cardiomyocytes. In CABG a weak expression of ICAM-1 was observed on endothelial cells but not on myocytes. VCAM-1 was expressed on vascular endothelium and perivascular infiltrating cells in HTX but not in CABG. VCAM-1 was not found to be expressed on myocytes. There was no evidence for the presence of E-selectin in any of our biopsy specimens. Our study shows that the study of cell adhesion molecules adds to the pathophysiological understanding of inflammation after transplantation in cardiac disease. This offers a potential for the development of diagnostic tools and new therapeutic strategies.

Biopsy↗
PubMed1996

The adhesion molecule E-cadherin and a surface antigen recognized by the antibody 9C4 are selectively expressed on erythroid cells of defined maturational stages.

The antigen expression of immature erythroid bone marrow cells was studied using two recently generated monoclonal antibodies (mAb), mAb 67A4 and 9C4, with specificities for the epithelial cell adhesion molecule E-cadherin (E-cad; mAb 67A4), and a novel 110 kDa differentiation antigen (mAb 9C4) with unknown molecular structure. Pappenheim staining of FACS-purified cells labeled with mAb 9C4 and anti-glycophorin A (GA) revealed that the majority of the 9C4+GA- and 9C4+GA+ cells consisted of erythroblasts. In contrast, the E-cad-positive population comprised normoblasts and erythroblasts. While the E-cad+GA- fraction contained mainly erythroblasts and basophilic normoblasts, the E-Cad+GA+ population was enriched in orthochromatic and polychromatophilic normoblasts. By colony assays of affinity column-purified cells it could be shown that erythroid colony forming units (CFU-E) were enriched and erythroid burst forming units (BFU-E) were depleted in the 9C4- and E-cad-positive fractions. Flow cytometric analysis of bone marrow cells double-labeled with mAb 67A4 and anti-CD71, anti-CD117, anti-CD34, or anti-GA revealed that about 90% of the E-cad-positive cells coexpressed CD71, about 70% were positive for CD117, about 50% for GA, and only about 5% coexpressed CD34. The expression pattern of 9C4 antigen was similar to that of E-Cad with the exception that only a minority of the 9C4-positive cells coexpressed GA. Lymphoid and myeloid markers were negative on both the E-Cad- and 9C4-positive populations. In these studies we describe the identification of a new mAb-defined antigen which is specifically expressed on erythroblasts and CFU-E(9C4) and demonstrate that E-Cad is not only expressed on epithelial cells but also on erythropoietic cells of defined maturational stages.

Antibodies, Monoclonal↗