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T Müller

Publications and source records attributed to T Müller.

At least 343 records · Page 19Linked to original sources

Further analysis of the mechanisms underlying the tracheal relaxant action of SCA40.

1. SCA40 (1nM-10 microM), isoprenaline (1-300 nM) and levcromakalim (100 nM-10 microM) each produced concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachea. Propranolol (1 microM) markedly (approximately 150 fold) antagonized isoprenaline but did not antagonize SCA40. The tracheal relaxant action of SCA40 was unaffected by suramin (100 microM) or 8-(p)-sulphophenyltheophylline (8-SPT; 140 microM). 2. An isosmolar, K(+)-rich (80 mM) Krebs solution increased tracheal tone, antagonized SCA40 (approximately 60 fold), antagonized isoprenaline (approximately 20 fold) and very profoundly depressed the log concentration-effect curve for levcromakalim. Nifedipine (1 microM) did not itself modify the relaxant actions of SCA40, isoprenaline or levcromakalim. However, nifedipine prevented the rise in tissue tone and the antagonism of SCA40 and isoprenaline induced by the K(+)-rich medium. In contrast, nifedipine did not prevent the equivalent antagonism of levcromakalim. 3. Charybdotoxin (100 nM) increased tracheal tone, antagonized SCA40 (approximately 4 fold) and antagonized isoprenaline (approximately 3 fold). Nifedipine (1 microM) prevented the rise in tissue tone and the antagonism of SCA40 and isoprenaline induced by charybdotoxin. 4. Quinine (30 microM) caused little or no change in tissue tone and did not modify the relaxant action of isoprenaline. However, quinine antagonized SCA40 (approximately 2 fold). Nifedipine (1 microM) prevented the antagonism of SCA40 induced by quinine. 5. Tested on spontaneously-beating guinea-pig isolated atria SCA40 (1 nM-10 microM) increased the rate of beating in a concentration-dependent manner. Over the concentration-range 1 microM-10 microM, SCA40 also caused an increase in the force of atrial contraction. 6. Intracellular electrophysiological recording from guinea-pig isolated trachealis showed that the relaxant effects of SCA40 (1 micro M) were often accompanied by the suppression of spontaneous electrical slow waves but no change in resting membrane potential. When the concentration of SCA40 was raised to 10 micro M, its relaxant activity was accompanied both by slow wave suppression and by plasmalemmal hyperpolarization.7. SCA40 (10 nM- 100 micro M) more potently inhibited the activity of cyclic AMP phosphodiesterase (PDE)than that of cyclic GMP PDE derived from homogenates of guinea-pig trachealis. Theophylline(1 micro M- 1O mM) also inhibited these enzymes but was less potent than SCA40 in each case and did not exhibit selectivity for inhibition of cyclic AMP hydrolysis.8. Tested against the activity of the isoenzymes of cyclic nucleotide PDE derived from human blood cells and lung tissue, SCA40 proved highly potent against the type III isoenzyme. It was markedly less potent against the type IV and type V isoenzymes and even less potent against the isoenzymes types I and II.9. It is concluded that the tracheal relaxant action of SCA40 (1 nM- 1 micro M) does not involve the activation of beta-adrenoceptors or P1 or P2 purinoceptors. Furthermore, this action is unlikely to depend upon the opening of BKca channels with consequent cellular hyperpolarization and voltage-dependent inhibition of Ca2+ influx. The tracheal relaxant action of SCA40 (up to 1 micro M) is more likely to depend upon its selective inhibition of the type III isoenzyme of cyclic nucleotide PDE. At concentrations above 1 micro M, SCA40 exerts more general inhibition of the isoenzymes of cyclic nucleotide PDE and may then promote the opening of BKca channels.

Animals↗

Palinopsia as sensory epileptic phenomenon.

Visual perseveration (VP) is defined as persistence or recurrence of visual images, when the stimulus is no longer present. We report three patients with occipital cortical lesions in the right hemisphere and VP. Electroencephalography showed epileptic abnormalities in all cases. In one patient synchronous electroencephalic recordings during the onset of palinopsia-a subtype of VP-revealed, that VP was associated with a clear cut right occipital seizure with a secondary diffusion of the discharge over both hemispheres, which has not been reported in combination with the onset of palinopsia heretofore. In all three patients sensory seizures have to be considered as probable cause of VP.

Adult↗

Plasma levels of the beta-carbolines harman and norharman in Parkinson's disease.

Several lines of evidence suggest that endogenous and exogenous toxins may play a major role in the pathogenesis of Parkinson's disease (PD). In vivo aromatic beta-carbolines, like harman or norharman, may easily be formed by cyclization of indoleamines with e.g. aldehydes. Because of the structural similarity to MPTP, beta-carbolines have been proposed as endogenous toxins. For further elucidation of the role of beta-carbolines in neurodegenerative disorders, harman and norharman plasma levels were measured in 36 patients with PD and compared to an age- and sex-matched control group. Plasma levels of norharman in PD were significantly higher compared to the control group. Harman in the plasma of Parkinsonian patients was also elevated compared to controls, but this difference was not significant. Correlation of beta-carbolines with plasma levels of L-dopa, oral doses of bromocriptine and selegiline in treated Parkinsonian patients showed no significant results. On the one hand these results may suggest a possible role of beta-carbolines in the pathophysiological processes initiating PD, by, e.g., inducing mitochondrial respiratory inhibition like MPP+. One may speculate, however, that elevated levels of norharman and harman are due to an endogenous upregulation caused by unknown metabolic processes.

Aged↗

Distorted color discrimination in 'de novo' parkinsonian patients.

We performed the Farnsworth-Munsell 100-hue test in 16 "de novo" patients with Parkinson's disease and 16 age-matched controls to determine their color discrimination ability. The mean total error score in patients was significantly elevated as compared with controls (64.6 in patients versus 16.0 in controls). We conclude that the impairment of color discrimination may be an early sign in Parkinson's disease.

Color Perception↗

[Not Available].

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Germany↗

Developmental regulation of ion channels and receptors on glial cells.

The electrophysiological properties of glial precursor cells and oligodendrocytes were studied in an intact tissue preparation, the corpus callosum slice, with the patch-clamp technique. The pattern of voltage-gated currents exhibited by different cell types in this white matter tract was compared with that from cultured cells of the O-2A lineage. Precursor cells from the in vitro and the in situ preparation were strikingly similar in most aspects. In contrast, oligodendrocytes in the intact tissue differed from their culture correlates and displayed the ability to redistribute excess K+. To study glial transmitter receptors in neuronglial interactions during development, Bergmann glial cells were investigated in a slice preparation of the cerebellum.

Animals↗

Antagonistic mutant proteins of interleukin-4.

Interleukin-4 is a major regulator of the immune system, directing e.g. induction of a TH2 phenotype in T-cells, activation of B-cells and synthesis of IgE type antibodies, which are associated with allergic responses. Site-directed mutagenesis has revealed two sites important for receptor interaction on IL-4: site I mediates binding to the IL-4 receptor alpha subunit, and site II is involved in signal transduction through the receptor complex. Specific mutations in site II produced a series of ligands which bound to the receptor with high affinity, but had little or no agonistic activity and inhibited effects of wild type IL-4. The closely related cytokine IL-13, also a mediator of allergic processes, is antagonized as well. Antagonistic site II mutants of human IL-4 are therefore effective inhibitors with therapeutic potential for IL-4 associated diseases like type I hypersensitivity and asthma.

Amino Acid Sequence↗

[Is insufflation with carbon dioxide as an ambulatory procedure for evaluating tubal patency obsolete today?].

UNLABELLED: Tubal insufflation with carbon dioxide is one of the ambulatory and non-invasive procedures in use for the evaluation of tubal patency. The aim of the present study was to investigate whether the findings obtained at tubal insufflation are reliable enough to avoid laparoscopy with instillation of dye for its inherent risk of severe operative complications. Diagnostic accuracy, positive and negative predictive value of tubal insufflation were compared with that of the reference method (laparoscopy) in 107 infertile patients of childbearing age without previous pelvic inflammatory disease, tubal or ovarian surgery. No result was obtained from tubal insufflation in 13 patients for intolerance or technical problems. The positive predictive value (percentage of correct positive findings, i.e., tubes patent) was 0.79 (130/165 tubes), the negative predictive value (percentage of correct negative findings) 0.43 (10/23) with an overall diagnostic accuracy (percentage of correct findings) of 0.74. If both tubes were reported patent on insufflation (68 patients), this finding was confirmed in 82% (56/68) on laparoscopy. The remaining 18% also include the rate of false negative findings (tubes falsely reported as occluded) on laparoscopy which may account for up to 10% according to the literature. False negative findings on insufflation were reported at a frequency of 21% (35/165 tubes). COMMENT: The diagnostic accuracy of tubal insufflation with carbon dioxide is definitely inferior to that of laparoscopy. In view of the frequency of false negative findings, its use as a screening procedure should be restricted to young patients with a low probability of tubal occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Psychoanalytic theories of hypochondria].

Although hypochondria is one of the earliest psychic conditions to be described, its nosological status is still uncertain and it has been largely neglected in theories of psychosomatics and neurosis. The authors undertake a detailed review of the literature and examine the psychodynamic concepts and theoretical approaches to the hypochondria phenomenon, from Freud, Ferenczi and Levy, through Klein and the ego psychologists, object-relation theories and the psychology of the self, all the way up to the present day. The authors trace the differences between hypochondria and other body-related disturbances and indicate the consequences for diagnosis and therapy.

Freudian Theory↗

[Patients of an ambulatory sleep center--critical variables of insomniacs].

The following study presents results of a broad diagnostical screening for 128 insomniacs, which includes polysomnography, sleep-wake diaries and psychosometrical testing. It was our special aim to investigate about critical but not classical variables for insomnia, which had been mentioned in sleep literature before. We therefore focused on hypotheses about the meaning of state 1 sleep (according to Zorick et al. 1984) and the number of REM-Non-REM Cycles (according to Rüther et al. 1985) for the diagnosis of insomnia. Statistical analysis (t-Test, p = 0.05) showed that patients with less than 3 REM-Non-REM Cycles consumed significantly more hypnotics during 6 months before the sleep examination. Moreover it was obvious (Chi-Square, p = 0.001) that more than 50% of insomniacs with organic causes presented less than 3 cycles, whereas the latter was true only for 1 patient with primary insomnia. Although results were not as strong for the "state-1 sleep variable", we find that these non-classical sleep variables should be sincerely regarded within the future context of the diagnosis of insomnia.

Adult↗

Exogenous stimulation of NGF synthesis by catecholamines and their analogues.

In humans different problems are associated with the direct application of neurotrophic factors like e.g. nerve growth factor (NGF). Therefore increasing attention has been focused on the concept of pharmacological stimulation of endogenous synthesis of trophic factors. For various compounds, especially catecholamines and their analogues, it has been demonstrated that induction of synthesis of NGF in glial and neuronal cells is possible. However, further experiments are necessary to confirm these results under in vivo conditions and to ensure safe and efficient clinical application.

Catecholamines↗

Neuroimmune mechanisms in Parkinson's disease.

The potential role of immune mechanisms in the pathogenesis of Parkinson's disease is still a matter of controversy. Both peripheral and central immunological disturbances have been reported. It is possible that this altered function of the immune system is responsible for autodestruction of neurons in Parkinson's disease and other neurodegenerative disorders. In this case possible neuroprotective therapeutic strategies could be developed. However, further investigations are necessary to elucidate the conditions of normal or pathologic interaction between the brain and the immune system.

Animals↗

Plasma harman and norharman in Parkinson's disease.

Several lines of evidence suggest that endogenous and exogenous toxins may play a major role in the pathogenesis of Parkinson's disease (PD). In the brain aromatic beta-carbolines, like harman or norharman, may be formed by cyclization of indoleamines. Because of the structural similarity to MPTP, beta-carbolines have been proposed as endogenous toxins. For further elucidation of the role of beta-carbolines in neurodegenerative disorders, harman and norharman plasma levels were measured in 36 patients with PD and compared to an age- and sex-matched control group. Plasma levels of norharman in PD were significantly higher compared to the control group. Harman in the plasma of Parkinsonian patients was also elevated compared to the controls, but this difference was not significant. On the one hand these results may suggest a possible role of beta-carbolines in the pathophysiological processes initiating PD. But on the other hand one may speculate that elevated levels of norharman and harman are due to an endogenous upregulation, caused by unknown metabolic processes to reduce oxidative stress by inhibiting e.g. monoaminooxidases in neurons.

Aged↗

Intravenous application of amantadine and antiparkinsonian efficacy in Parkinsonian patients.

The aim of this study was to estimate the pharmacokinetic properties of amantadine after infusion and subsequent peroral application of two galenic forms at a daily dose of 200 mg. In addition, the pharmacodynamics of the different treatment regimes evaluated by the motoric items of the UPDRS were investigated. Furthermore, the relationship between plasma levels and clinical efficacy was evaluated. To address these questions Parkinsonian patients were randomly assigned to 3 groups: infusion-tablet, infusion-capsule, infusion-infusion. Parenteral application of amantadine sulphate provided a rapid improvement in Parkinsonian patients within the first three days. This response could be stabilized and even improved further by peroral treatment for another 3 days. The change from intravenous to peroral tablet therapy was followed by a transient decrease in cmax and AUC(o-t) being not reflected by a reduction in clinical efficacy. Conversely, a persistent reduction of the plasma concentration after switching to the capsule therapy was paralleled by a somewhat unfavourable clinical response.

Administration, Oral↗

Cell manipulation and cultivation under a.c. electric field influence in highly conductive culture media.

Extreme miniaturisation of electrodes enabled us to apply high-frequency electric fields (between 100 kHz and several hundred MHz) of field strengths up to 50 kV/m into cell suspensions of high conductivity (several S/m), such as original cell culture media. The active electrode areas were additionally decreased and modified by insulating the terminals and/or coating of the electrodes with thin dielectric layers. Micro scaled electrode structures were fabricated on glass or silicon wafers in semiconductor technology. It could theoretically and experimentally be shown that cells exhibit exclusively negative dielectrophoresis if suspended in highly conductive media. Therefore, they can be repulsed from surfaces by appropriate arrangements of electrodes and easily be manipulated in free solution. Adherently growing animal cells, like mouse fibroblasts (3T3, L929), were cultivated in Dulbecco's Modification of Eagle's Medium (DMEM) or RPMI 1640 under permanent field application (frequency: 10 MHz, field strength: 50-100 kV/m).

3T3 Cells↗

RAP1 stimulates single- to double-strand association of yeast telomeric DNA: implications for telomere-telomere interactions.

Repressor Activator Protein 1 (RAP1) of Saccharomyces cerevisiae is an abundant nuclear protein implicated in telomere length maintenance, transactivation, and in the establishment of silent chromatin domains. The RAP1 binding site 5' of the yeast HIS4 gene is also a region of hyperrecombination in meiosis. We report here that as RAP1 binds its recognition consensus, it appears to untwist double-stranded DNA, which we detect as the introduction of a negative supercoil in circularization assays. Coincident with the RAP1-dependent untwisting, we observe stimulation of the association of a single-stranded yeast telomeric sequence with its homologous double-stranded sequence in a supercoiled plasmid. This unusual distortion of the DNA double helix by RAP1 may contribute to the RAP1-dependent enhancement of recombination rates and promote non-duplex strand interactions at telomeres.

Base Sequence↗