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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 235 records · Page 13Linked to original sources
PubMed1998

N-arylrolipram derivatives as potent and selective PDE4 inhibitors.

Derivatization of rolipram led to the identification of 3-[4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]-5-( 3- methoxybenzyloxy)-benzoic acid N',N'-dimethylhydrazide (4), a potent and selective inhibitor of PDE4, which inhibits the activation of human leukocytes with pIC50 values in the range of 7.3-7.8, and blocks antigen induced eosinophilia in Brown Norway rats at a dose of 1 mg/kg (i.t.).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

[Intraepidermal free nerve fiber endings and their importance for cutaneous pain].

INTRODUCTION: Former studies performed by means of supravital methylene blue (MB) staining could demonstrate intraepidermal free nerve fiber endings (FNE). Unfortunately, these publications were only illustrated by drawings. Furthermore, the practical details of the method were only insufficiently handed down to posterity. Therefore, a modification of the staining procedure should be worked out for this purpose. Subsequently, the possible advantages of the method compared with common histochemical techniques should be clarified. Regarding the possible nociceptive functions of the FNE, the corresponding conclusions should be drawn from the results. METHODS: The dye was injected subepidermally into the hairless skin of the palmar- and plantar sites of rat paws followed by light microscopy. RESULTS: 2 different morphological types of FNE could be detected within the epidermis. The thick FNE, which occurred less frequently than the thin ones (approximately 20/mm(2) in relation to 1000/mm(2)), represented nerve fiber branches ascending up to the granular layer where they formed superficial plexus (Figs. 1 and 3b). In contrast to the thick FNE, the thin ones were varicose and unbranched (Figs. 2 and 3a). CONCLUSIONS: Regarding the demonstration of morphological details, especially the branching pattern and the thickness of FNE, MB-staining achieves interesting results. The visualization of 2 different types of FNE within the epidermis extends the validity of the concept of punctate sensibility into this skin layer. Both types of FNE have to be functionally connected with different sensoric tasks. Possibly, a subpopulation of the thin FNE might be identical to the substance P-immunoreactive one which is wellknown to possess primarily a nociceptive function.

English Abstract↗
PubMed1998

Characterisation of pseudorabies virus isolated from wild boar (Sus scrofa).

Seroepidemiological evidence had suggested that pseudorabies (Aujeszky's disease) virus (PrV) infections occur in the European wild boar population in eastern Germany, although attempts to isolate the causative agent had failed. In 1995 and 1996, five virus isolates were recovered from latently infected wild boar originating from two regions where the disease was endemic. The isolates were identified as PrV by immunofluorescence and neutralisation with specific sera and grouped as PrV type I. Compared with reference strains and PrV isolates obtained from domestic animals in the same region, considerable differences in the DNA patterns were detected. In particular, two additional larger BamHI-DNA fragments migrating in agarose gel electrophoresis between fragments 3 and 4 were observed, accompanied by the loss of fragments 5, 10 and 12. Southern blot hybridisation with fragment-specific DNA probes identified the larger fragments as fusions of BamHI-fragments 5 and 10, and 5 and 12, respectively, due to a loss of a BamHI-site in the inverted repeat regions. This distinctive fragment pattern has so far not been observed in PrV isolates from domestic pigs in Germany.

Animals↗
PubMed1998

[A case of Carney complex].

HISTORY AND CLINICAL FINDINGS: For some months a 57-year-old woman had noted increasing shortness of breath, associated in the last few weeks with undirected vertigo and several brief periods of lost consciousness. She was finally admitted because of additional central facial paresis. On auscultation a high-frequency systolic murmur was heard over the apex and a discrete diastolic murmur over Erb's point. There were numerous facial freckles and three cutaneous myxomas. INVESTIGATIONS: Echocardiography revealed irregular tumours throughout the left atrium and a large broad-based one prolapsing through the mitrale valve in diastole. Computed tomography demonstrated a 6 x 6 cm tumour in the left lower abdomen, probably arising from the left ovary, and a second 3 x 3 cm presacral tumour. TREATMENT AND COURSE: At cardiac surgery four tumours were found in the left atrium and resected: histologically they were benign myxomas. Removal required extensive resection in the area of the interatrial septum and the atrial wall, resulting in 2 degrees AV block for which a VDD pacemaker was implanted. CONCLUSION: Atrial myxomas may be the cardinal sign of the Carney Complex, an autosomal dominant syndrome with cutaneous myxomas, myxoid abdominal tumours, hormone-producing tumours in the testicles, adrenal cortex or hypophysis, schwannoma as well as lentigines. For this reason, further tumours should be looked for if freckles and/or cutaneous tumours are found in association with an atrial myxoma. The patient and family should be informed about the genetic aspects.

Dyspnea↗
PubMed1998

Tenascin is a useful marker in the diagnosis of inflammatory myopathies.

The expression of tenascin, NCAM, vimentin and HSP-70 was examined in 15 patients with dermatomyositis and 12 patients with polymyositis. All biopsies with dermatomyositis showed a confluent network of tenascin expression in the extracellular space. This network surrounded numerous fibers (39 up to 320). Tenascin expression preceded other histological and immunohistochemical signs of dermatomyositis such as the expression of N-CAM and vimentin and the appearance of perifascicular atrophy and inflammatory response. Tenascin expression was found in 3 biopsies where microtubular inclusions in the arteriolar walls were absent. In contrast, tenascin expression was confined to the surroundings of necrotic fibers also expressing vimentin or N-CAM in polymyositis. In general, tenascin was found in the vicinity of inflammatory cells, only. These findings suggest that tenascin is induced by ischemic stress in dermatomyositis. Widespread tenascin expression in a fascicular distribution is a specific marker, if an inflammatory myopathy has been proven by standard techniques. In some cases, tenascin staining might confirm the clinical diagnosis of dermatomyositis, where other histological findings are inconclusive.

Adolescent↗
PubMed1998

Chance and risk of controlling rabies in large-scale and long-term immunized fox populations.

The large-scale immunization of European fox populations against rabies is currently under the microscope for reducing the considerable expenditure without putting public health at risk. Empirical knowledge is inadequate to interpret the lasting sporadic incidences and, therefore, to verify the final success of the immunization campaigns. By using a proven simulation model we show that rabies can persist on a very low level in the form of spatio-temporal moving infection clusters within a highly immunized fox population. We found further: (i) the existence of a threshold after which the chance of eradicating the disease by vaccination increases clearly, and (ii) that at least six years of 70% mean immunization rate are required to guarantee a likely success.

Animals↗
PubMed1998

Kleine-Levin syndrome and Parkinsonian symptoms--a case report.

We report the case of a 54-year-old male patient, who developed the symptoms of Kleine-Levin syndrome (KLS) at the age of fifty. Four years later Parkinsonian symptoms (PS) appeared. The possible relationship between both KLS and PS, e.g. regarding neuroendocrinological similarities, will be discussed to explain the subsequent onset of PS after the manifestation of KLS in this patient.

Humans↗
PubMed1998

Selegiline as immunostimulant--a novel mechanism of action?

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties.

Adjuvants, Immunologic↗
PubMed1998

Colour vision abnormalities do not correlate with dopaminergic nigrostriatal degeneration in Parkinson's disease.

Sensory disturbances such as olfactory or visual dysfunctions are common in Parkinson's disease (PD). A possible relationship between distorted colour discrimination and the nigrostriatal dopamine deficit is still a matter of debate. We examined 31 de novo Parkinsonian patients with [123I]beta-CIT single photon emission tomography (SPECT). We used a single-head gamma-camera and calculated the binding ratio striatum/cerebellum (specific/nonspecific binding) of [123I]beta-CIT uptake. On the same day, we performed the Farnsworth-Munsell 100 Hue Test (FMT) in these patients and estimated the total error score, in order to investigate abnormalities of colour vision. Parkinsonian patients' total error score was higher compared with an age- and sex-matched control group (P = < 0.0001), whereas disability scores of the Hoehn and Yahr scale (P = 0.019, Spearman r = 0.419) and the Unified Parkinson's Disease Rating Scale (P = 0.039, Spearman r = 0.373) correlated with total error score. No significant association appeared between total error score (Spearman r = -0.119, P = 0.525) and [123I]P-CIT-SPECT ratio. Thus both total error scores of the FMT and [1231]beta-CIT-SPECT binding ratios have been found to reflect the severity of PD. However, only [123I]beta-CIT SPECT reflects degeneration of dopaminergic neurons of the basal ganglia, but does not reflect alterations of the visual system and/or extranigral lesions in PD. From our results, we speculate that FMT may be a valuable clinical method to measure extranigral lesions of the visual system in PD.

Adult↗
PubMed1998

Plasma levels of R- and S-salsolinol are not increased in "de-novo" Parkinsonian patients.

An augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL) or an increased N-methylation of these compounds has been addressed by various investigators as putative pathophysiologic mechanisms in Parkinson's disease (PD). Aim of this study was (1) to investigate putative relations between plasma levels of dopamine and R- and S-enantiomers of SAL and (2) whether these metabolic precursors of the neurotoxic N-methylated-SAL (NMSAL) are elevated in untreated "de-novo" Parkinsonian patients compared to age- and sex-matched healthy controls. Plasma levels of R- and S-SAL and dopamine did not significantly (R-SAL: p=0.61, S-SAL: p=0.51, dopamine: p=0.84) differ in both groups. Parkinsonian patients' R-SAL plasma levels were inversely related to intensity (p=0.03, r =-0.42) and duration of PD (p=0.03, r=-0.43) in contrast to S-SAL and dopamine. Dopamine levels were not associated to R-SAL (p=0.88, r2=0.0008) and S-SAL (p=0.088, r2=0.12) neither in Parkinsonian patients nor in controls. We conclude, that an upregulation of N-methylation of tetrahydroisoquinolines takes place in PD by enzymes such as neutral N-methyltransferase specific for R-SAL. The activity of this enzyme has been found elevated in parkinsonian lymphocytes. This increased N-methylation by the N-methyltransferase specific for R-SAL leads to the known augmented levels of neurotoxic R-NMSAL in Parkinsonian patients compared to controls in the cenral nervous system especially in the beginning of PD.

Adult↗
PubMed1998

Numerical methods to determine calcium release flux from calcium transients in muscle cells.

Several methods are currently in use to estimate the rate of depolarization-induced calcium release in muscle cells from measured calcium transients. One approach first characterizes calcium removal of the cell. This is done by determining parameters of a reaction scheme from a fit to the decay of elevated calcium after the depolarizing stimulus. In a second step, the release rate during depolarization is estimated based on the fitted model. Using simulated calcium transients with known underlying release rates, we tested the fidelity of this analysis in determining the time course of calcium release under different conditions. The analysis reproduced in a satisfactory way the characteristics of the input release rate, even when the assumption that release had ended before the start of the fitting interval was severely violated. Equally good reconstructions of the release rate time course could be obtained when the model used for the analysis differed in structure from the one used for simulating the data. We tested the application of a new strategy (multiple shooting) for fitting parameters in nonlinear differential equation systems. This procedure rendered the analysis less sensitive to ill-chosen initial guesses of the parameters and to noise. A locally adaptive kernel estimator for calculating numerical derivatives allowed good reconstructions of the original release rate time course from noisy calcium transients when other methods failed.

Algorithms↗
PubMed1998

The muskrat (Ondatra zibethicus) as a new reservoir for puumala-like hantavirus strains in Europe.

We have used an indirect immunofluorescent assay (IFA) and reverse transcription-PCR (RT-PCR) to screen the sera and tissues of muskrats (Ondatra zibethica) caught in the northwest of Brandenburg and in the northeast of Saxony-Anhalt, Germany, for hantavirus infection. Kidney and/or lung tissue from 6 (3.1%, CI = 1.1-6.5%) out of 197 muskrats were found to be positive for genomic sequences of hantavirus by RT-PCR. We could also demonstrate that 14 (5%, CI = 2.9-8.7%) out of 266 muskrat's sera available for testing contained hantavirus-specific antibodies in IFA. Thus, a total of 8% of the investigated muskrat population was found to be positive for hantavirus infection by RT-PCR and IFA. None of the animals was found positive in both tests. Further analysis of the RT-PCR amplified fragments by genomic sequencing revealed sequences mostly related to the puumala (PUU) S segment sequence of the Hällnäs B1 hantavirus strain (97-99% similarity). Our data therefore demonstrate that Ondatra zibethicus serves as an additional reservoir for puumala-like hantavirus strains in Europe. The epidemiological implications of this finding for hantavirus infection in Europe and elsewhere are discussed.

Amino Acid Sequence↗
PubMed1998

Contractility and inhibition of protein phosphatases by cantharidin.

1. Cantharidin is a natural defensive toxicant produced by blister beetles. 2. Cantharidin shares structural similarity with highly toxic commercial herbicides (e.g., endothall, endothall anhydride and endothall thioanhydride). 3. Cantharidin inhibits the activity of purified catalytic subunits of serine/threonine protein phosphatases (PP) type 1 and type 2A. 4. Cantharidin increases force of contraction in isolated myocardial and vascular preparations. 5. Cantharidin enhances the phosphorylation state of myocardial and vascular regulatory proteins. 6. Cantharidin is a valuable tool for studying the function of PP in regulatory phosphorylation-dephosphorylation events.

Animals↗
PubMed1998

A novel organotypic long-term culture of the rat hippocampus on substrate-integrated multielectrode arrays.

Spatiotemporally coordinated activity of neural networks is crucial for brain functioning. To understand the basis of physiological information processing and pathological states, simultaneous multisite long-term recording is a prerequisite. In a multidisciplinary approach we developed a novel system of organotypically cultured rat hippocampal slices on a planar 60-microelectrode array (MEA). This biohybrid system allowed cultivation for 4 weeks. Methods known from semiconductor production were employed to fabricate and characterize the MEA. Simultaneous extracellular recording of local field potentials (LFPs) and spike activity at 60 sites under sterile conditions allowed the analysis of network activity with high spatiotemporal resolution. To our knowledge this is the first realization of hippocampus cultured organotypically on multi-microelectrode arrays for simultaneous recording and electrical stimulation. This biohybrid system promises to become a powerful tool for drug discovery and for the analysis of neural networks, of synaptic plasticity, and of pathophysiological conditions such as ischemia and epilepsy.

Action Potentials↗
PubMed1998

Platelet monoamine oxidase B activity in "de novo" and l-dopa treated parkinsonian patients and controls.

OBJECTIVE: Previous studies demonstrated controversial results regarding monoamine oxidase B (MAO-B) activity in platelets in the periphery in parkinsonian patients (PD). SUBJECTS AND METHODS: Therefore we determined platelet MAO-B activity in three age- and sex-matched groups of 17 untreated, so called "de novo" patients with Parkinson's disease (PD), 17 parkinsonian patients, receiving levodopa, and 17 controls by a radio enzymatic assay. RESULTS: No significant differences of MAO-B activity appeared. CONCLUSION: This result suggests that phenotypic determination of MAO-B activity in platelets may not be used as peripheral marker in PD and that levodopa treatment does not alter MAO-B activity in the periphery.

Aged↗
PubMed1998

Survey on viral pathogens in wild red foxes (Vulpes vulpes) in Germany with emphasis on parvoviruses and analysis of a DNA sequence from a red fox parvovirus.

The seroprevalence of canine parvovirus (CPV), canine distemper virus (CDV), canine adenovirus (CAV) and canine herpesvirus (CHV) infections in red foxes (Vulpes vulpes) was determined in fox sera collected between 1991 and 1995. A total of 500 sera were selected and the seroprevalences were estimated to be 13% (65 of 500 sera) for CPV, 4.4% (17 of 383 sera) for CDV, 35% (17 of 485 sera) for CAV, and 0.4% (2 of 485 sera) for CHV, respectively. No statistically significant differences were observed between the two (rural and suburban) areas under study. Parvovirus DNA sequences were amplified from tissues of free-ranging foxes and compared to those of prototype viruses from dogs and cats. We report here a parvovirus sequence indicative of a true intermediate between the feline panleukopenia virus-like viruses and the canine parvovirus-like viruses. The red fox parvoviral sequence, therefore, appears to represent a link between those viral groups. The DNA sequence together with a significant seroprevalence of parvovirus infections in foxes supports the hypothesis that the sudden emergence of canine parvovirus in the domestic dog population may have involved the interspecies transmission between wild and domestic carnivores.

Adenoviruses, Canine↗