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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 325 records · Page 18Linked to original sources

Morphological differences among nerve fiber endings in the rat oral mucosa as revealed by methylene blue staining.

The nerve fiber distribution in the oral mucosa of the soft palate and palatoglossal arch of the rat was studied by means of methylene blue supravital staining. It was focused primarily on the dye uptake of intraepithelial nerve fibers. Differences in the morphology of nerve fiber terminations were found between these regions of the oral mucosa. In the soft palate, local accumulations of intraepithelial nerve fibers which branched and showed terminal enlargements were detected. Intra- and perigemmal nerve fibers of chemosensory corpuscles could be stained. In the palatoglossal arch, numerous elongated papillae were seen containing nerve fiber plexus showing a complicated arborization pattern. In part, the collaterals penetrated the epithelium. The soft palate contained only a small number of lower but broader papillae which were covered by a more expanded intraepithelial nerve fiber plexus. In both regions, anastomoses between the branches of single nerve fibers were sometimes seen. Solitary delicate nerve fiber endings were loosely distributed throughout the epithelia. In addition, intrapapillar nerve endings, which were enclosed by a slightly stained capsule, were intensely stained; they showed characteristic lateral protuberances. The Merkel's discs were visualized as the components of a terminal network of nerve fiber branches. The observed differences in the shape and locations of the nerve terminations suggest different functions of these nerve fibers. Due to the low costs of the staining procedure and its ease in handling, it is well-suited for a mapping of the innervation pattern of the whole oral mucosa.

Animals↗

Chromatic and achromatic visual evoked potentials in Parkinson's disease.

Chromatic and achromatic visual evoked potentials (VEP) were evaluated in 39 patients with idiopathic Parkinson's disease (PD) (age 64.0 +/- 8.6 years) and 43 healthy controls (age 62.8 +/- 8.7 years). The following pattern-reversal checkerboard stimuli were performed: (1) achromatic with luminance contrast 86% (achr.hk.) (2) achromatic with luminance contrast 20% (achr.lk.); (3) chromatic isoluminant blue-yellow (by.); (4) chromatic isoluminant red-green (rg.). The mean latencies N70, P100, and N135 of chromatic and achromatic VEP were significantly delayed in patients with PD as compared to controls. The highest rate (41.0%) of pathological findings could be demonstrated by achromatic stimulation (luminance contrast 86%). Isolated abnormalities of chromatic VEP (in combination with normal achromatic VEP) were found in 5 (12.8%) patients. The delay of VEP-latencies was significantly correlated with the severity of motor symptoms in PD patients. We conclude that VEP are valuable tools to demonstrate a dysfunction of the visual system in PD. Although chromatic VEP are less sensitive than achromatic VEP, the combination of both will increase the diagnostic yield. Therefore, there seems to exist a variety of individual characters of visual impairment in PD.

Adult↗

[Restitutive effect of sleep on chronic performance stress].

During a polysomnographic (2 nights) sleep registration of 5 chronically stressed compared to 5 control persons 24 h blood cortisol values and salivary cortisol at daytime were measured and compared with measured stress vulnerability. While daytime cortisol levels were reduced under stress conditions, during night sleep combined with a significant change in sleep architecture cortisol excretion raised markedly compared to controls, and the cortisol response to CRF provocation is no more blunted but activated beyond controls, demonstrating the restitutive and protective effect of sleep.

Adaptation, Psychological↗

Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients.

Interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and interleukin-6 (IL-6) were measured in the cerebrospinal fluid (CSF) and plasma of 12 control subjects, 11 sporadic Alzheimer's disease (AD) and 22 de novo Parkinson's disease (PD) patients using high sensitivity enzyme-linked immunosorbent assays (ELISA). IL-1 beta and IL-6 contents were significantly elevated in the CSF of de novo PD and AD patients in comparison to the control group. In contrast, the plasma levels were not significantly affected. IL-2 contents in the CSF and plasma samples were unchanged in the three groups compared. Because the two cytokines IL-1 beta and IL-6 are known to play a key role in the interaction between the nervous and immune system, e.g. in the so-called acute phase response, our results support the involvement of immunological events in the complex process of neurodegeneration in AD and PD.

Adult↗

Inhibitors of type IV phosphodiesterases reduce the toxicity of MPTP in substantia nigra neurons in vivo.

The neuropathology of Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra. We have recently shown that the activation of protein kinase A improves the survival of dopaminergic neurons in culture and, furthermore, protects them from the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) in vitro. We have now analysed the potential of phosphodiesterase inhibitors to increase cAMP levels in dopaminergic neurons, to improve their survival in culture and to protect them from the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. Increasing intracellular cAMP with phosphodiesterase type IV-specific inhibitors enhanced the survival of dopaminergic neurons in culture. Inhibitors of other phosphodiesterase types were not active. In vivo, phosphodiesterase type IV inhibitors reduced the MPTP-induced dopamine depletion in the striatum of C57BL/6 mice. Furthermore, the loss of tyrosine hydroxylase-immunopositive neurons in the substantia nigra of these animals was diminished. After Nissl staining, a similar reduction of the MPTP-induced loss of neurons was observed in the substantia nigra. The protective effect of protein kinase A activation did not appear to be due to the blocking of MPP+ uptake into dopaminergic neurons. This was not decreased after treatment with forskolin or 8-(4-chlorophenylthio)-cAMP. Thus, protein kinase A regulates the survival and differentiation of dopaminergic substantia nigra neurons in vivo, implicating a therapeutic potential for substances which regulate cAMP turnover in these neurons.

Animals↗

Quantification and mapping of antigenic determinants of serum amyloid A (SAA) protein utilizing sequence-specific immunoglobulins and Eu3+ as a specific probe for time-resolved fluorometric immunoassay.

Serum amyloid A (SAA) protein, the most prominent amongst acute-phase proteins, is the specific precursor protein of secondary reactive amyloidosis. The fact that SAA once released into the circulation as a 'free' protein rapidly associates with lipoproteins of the high-density range indicates a specific role in lipoprotein metabolism. In this study a new sensitive assay for quantification of human SAA protein in biological specimens using affinity-purified polyclonal antibodies and Eu3+ as a specific probe for time-resolved fluorometric immunoassay is presented. Both purified SAA and SAA-rich high-density lipoprotein particles served as reliable standards in the indirect and the direct sandwich dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA). The detection limit of the DELFIA technique presented was 4-10 ng after sample dilution of 1/2500. The intra-assay coefficient of variation averaged 4.3% whereas the inter-assay coefficient of variation averaged 6.2%. Comparison with the nephelometric assay, a widely and commonly used assay for SAA quantification in plasma, revealed correlation coefficients of 0.9428. In addition to polyclonal anti-human SAA antibodies sequence-specific antibodies raised against synthetic peptides corresponding to region; 1-17, 14-30, 27-44, 40-63, 59-72, 68-84, 79-94, and 89-104 of the human SAA amino acid sequence were studied. Sequence-specific antibodies raised against epitopes 27-44, 59-72, 68-84, and 89-104 recognize human SAA protein in the DELFIA assay whereas antibodies raised against epitopes 1-17, 14-30, 40-63 and 79-94 failed to recognize the corresponding epitopes. Results obtained from these studies indicate that the N-terminal domain (1-30) as well as epitopes 40-63 and 79-94 of human SAA are apparently masked by the environment of the lipoprotein particle. From our studies it is proposed that the epitopes 31-39, 64-78, and 95-104 may be responsible for the interaction of SAA-rich high density lipoprotein particles with peripheral cells.

Antibodies, Monoclonal↗

Expression of c-fos in quiescent Swiss 3T3 cells exposed to aqueous cigarette smoke fractions.

The exposure of quiescent Swiss 3T3 cells to mainstream cigarette smoke (CS) trapped in PBS solution (smoke-bubbled PBS) resulted in the dose-dependent expression of c-fos mRNA and protein. Kinetic investigations revealed that in contrast to mitogens, which strongly but transiently induce the c-fos promoter within minutes, c-fos transcripts in cells exposed to 0.03 puffs (approximately 1 cm3) of CS/ml of medium accumulated slowly but were still seen after 8 h; the maximum expression rates were between 2 and 6 h of exposure. This specific expression pattern appears to be the result of altered posttranscriptional as well as transcriptional regulation, since a strikingly increased stability of the c-fos message (t1/2, > or = 2 h versus < 20 min in serum-stimulated cells) in smoke-treated cells was observed in addition to slight transcriptional activation of the c-fos promoter. CS-dependent DNA damage can be excluded as the only source for this altered expression pattern, since inhibition of DNA strand break formation by either catalase or o-phenanthroline had no detectable effect on the CS-induced c-fos expression. The results described here, and other CS-dependent cellular and biochemical effects, are similar to those induced in vitro by okadaic acid, a specific inhibitor of cell growth-regulatory protein phosphatases 1/2A (PP-1/2A). Hence, the effects of smoke treatment on these key enzymes were compared to those of okadaic acid based on the ability of cell-free extracts to release radiolabeled phosphate from glycogen phosphorylase a, a substrate of PP-1/2A. Results from these experiments indicate that both treatments inhibited PP-1/2A in a concentration- and analogous time-dependent manner. The data presented suggest that PP-1/2A may, at least in vitro, be targeted by water-soluble active compounds present in cigarette smoke.

3T3 Cells↗

Human interleukin-4 and variant R88Q: phasing X-ray diffraction data by molecular replacement using X-ray and nuclear magnetic resonance models.

The structure of recombinant human interleukin-4 (hIL-4) has been determined by both NMR and X-ray diffraction methods in several laboratories, including ours. The X-ray and NMR structures were successfully applied for solving the X-ray crystal structure by molecular replacement. Due to the small size of the hIL-4 molecule (129 residues) and its lack of structural diversity (4-helix bundle), this task was especially difficult and required special care with rotation function applications. The crucial point was that proper removal of the Patterson origin peaks was indispensable in all cases. All available structures of hIL-4 were checked, in a standardized procedure, for their suitability as templates for molecular replacement. The models derived from the various structures are close to, but not in all loop details identical with, the genuine X-ray structures. The deviations of the X-ray structure-derived models are of the same magnitude as the differences between the original X-ray structures, while the deviations of the NMR structure-derived models are two to three times as large. The hIL-4 variant R88Q is a binding mutant, its affinity to the receptor is decreased by a factor of about 200. Its X-ray structure was determined by molecular replacement using the wild-type X-ray structure determined in our laboratory as a model. The structure of R88Q is virtually identical with that of the wild-type protein. All differences besides the shortened side-chain of residue 88 occur at surface residues with high temperature factors, i.e. at spots where the structure is not well defined. Since the structure is not perturbed, the biological effect of decreased receptor affinity has to be attributed to the loss of a single positive charge in the surface area of the main receptor contact.

Computer Simulation↗

Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C).

We have recently reported increased survival of dopaminergic substantia nigra neurons by inhibition of phosphodiesterase type IV enzymes. As a first step to unravel the involvement of PDE IV subtypes in this process, we isolated phosphodiesterase type IV cDNAs from human substantia nigra. One isolated partial cDNA clone was most homologous to the partially cloned rat and human PDE IV-C isogene. Distribution analysis revealed that the enzyme is expressed in various tissues but not in cells of the immune system. Isolation of the full-length human PDE IV-C isogene cDNA and expression in a PDE-deficient yeast strain resulted in functional complementation of the yeast heat shock response. Inhibition of the enzymatic activity by rolipram characterized this enzyme as a typical type IV phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of aspartame on 45Ca influx and LDH leakage from nerve cells in culture.

Aspartame (ASM), an artificial sweetener, was shown to dose dependently increase 45Ca-influx into and lactate dehydrogenase (LDH) leakage from murine brain cell cultures. Astrocytes were more resistant than neurones to the effects of ASM. In cerebellar granule neurones, a 20% increase in calcium was found after an incubation time of 22 h in the presence of 0.1 mM ASM; at 0.5 mM concentration, calcium influx increased 40% compared with control cultures. At a concentration of 10 mM, influx was increased 13-fold after 5 h. Morphological appearance as judged by phase contrast microscopy was first visibly affected after exposure to 1 mM ASM for 22 h. Citrate, another food additive, was included in the study to demonstrate that cerebellar granule neurones could tolerate 10 mM additions to the medium and citrate did not cause 45Ca influx or morphological changes in neurones after 22 h. LDH leakage, a sign of severe cell damage, was observed at 1 mM concentrations of ASM after 22 h. Cerebral astrocytes on the other hand were more resistant and showed morphological changes, increased calcium influx and LDH leakage first at 5 mM concentrations of ASM.

Animals↗

Light and electron microscopical demonstration of methylene blue accumulation sites in taste buds of fish and mouse after supravital dye injection.

Electron microscopical data regarding methylene blue staining of taste buds in the epithelia of the goldfish lip and the cirumvallate papilla of the mouse tongue after supravital dye application are presented for the first time. The ultrastructural details were compared with the corresponding light microscopical findings. The dye was applied in different concentrations by injection or in crystalline from directly to the surface of the tissues. Both methylene blue and tissue were simultaneously fixed by immersion in a paraformaldehyde-glutaraldehyde solution with the addition of phosphomolybdic acid. The ensuing dye precipitate was further stabilized by ammonium heptamolybdate. On the light microscopical level, the taste bud's receptive structures, i.e. the receptor area (fish) and the taste pit (mouse), exhibited the highest affinity for the dye. Additionally, the mucous material within the trenches around the circumvallate papillae in mice was intensely stained. On the electron microscopical level, the cationic phenothiazine dye bound to the receptor villi or to the mucus coating the receptive structures. In the case of higher dye concentrations, a staining of single taste bud cells took place starting apically and proceeding down to the base. Dye accumulations within the intercellular clefts between the epithelial cells or within other structures were observed only if the dye concentration was further increased. Since similar results were also obtained with the cationic phenazo dye Janus green, dye accumulation in the mucus covering the receptor villi may be representative of the general binding of organic cations, which are known to induce bitter taste sensations.

Animals↗

[Partnership and sex behavior of consumers of illegal drugs: a survey of 654 persons in the "open" drug scene in Zurich].

In the spring of 1991, a survey was carried out in the "open" drug scene in Zürich's Platzspitz area with the objective of studying drug users' behaviour with regard to relationships and sexuality, a random sample of 654 users (both male and female) of illegal drugs being interviewed and the data drawn from these interviews being compared with corresponding data on average young adults aged 17 to 30. The latter data have been continuously collected since 1986 to evaluate Switzerland's strategy to prevent AIDS. About fifty per cent of drug users are in steady relationships, which is a smaller proportion than among average young adults. On the other hand, occasional sexual contacts (whether or not a steady relationship exists) are three times as frequent among drug users. The use of condoms is slightly more frequent here than among the average population, but is not as yet-and especially among those who are HIV-positive-consistent enough by any means. The influence of drug abuse on sexuality is usually felt to be negative (decline in libidinal energy, impotence), and often brings about a decrease in sexual contacts. This is equally true of both opiates and stimulants (cocaine, amphetamine). Promiscuous behaviour is rare as such and does not occur with any greater frequency than among the average population. However, a large proportion of drug users is at some stage exposed to prostitution. In summary, one can say that the preventive strategy continues to be deficient where the sexual activities of drug users are concerned. A greater effort should be made, in this context, to target the following groups: persons already frequenting advice centers, persons who are HIV-positive, and male prostitutes.

Adolescent↗

A seroepidemiological survey for orthopox virus in the red fox (Vulpes vulpes).

703 blood samples from red foxes (Vulpes vulpes) were investigated to determine the prevalence of antibody against an orthopox virus (vaccinia virus strain Elstree). A blocking-ELISA based on a neutralizing monoclonal antibody was used. In this assay 46 sera (6.5%) were positive with titers of 1:2 to 1:16. ELISA-results were confirmed by the plaque reduction test with 44 of the 46 sera reacting positively. The specificity of antibodies in 21 selected sera was also demonstrated by Western blot analysis.

Animals↗

Physiology of Bergmann glial cells.

While Bergmann glial cells play an important role in the development of the cerebellum they were thought to serve as passive insulators of the Purkinje cell dendritic tree and its synaptic connections. New results challenge this view and demonstrate that Bergmann glial cells are equipped with a large repertoire of receptors allowing them to sense the activity of synapses. These receptors have distinct biophysical and pharmacological features activating second-messenger pathways in the Bergmann glial cells. It is evident that the synapse has to be viewed as consisting of three elements, the presynaptic and postsynaptic region and the glial ensheathment. All three elements of this synaptic complex may undergo plastic changes as a prerequisite for central nervous system plasticity. Glial cells could interfere with synaptic transmission by communicating with neurons via the extracellular space, e.g., by modulating ion concentrations or transmitter levels in the cleft (Fig. 6).

Animals↗

Color vision in Parkinson's disease: missing influence of amantadine sulphate.

In recent studies, disorders of chromatic and achromatic vision in parkinsonian patients have been demonstrated; these could be partially restored after application of L-Dopa. In this study, the effect of a 3-day infusion therapy with amantadine sulphate on color vision was evaluated in 19 parkinsonian patients by use of the Farnsworth-Munsell 100-Hue test. Under this treatment, the motor symptoms of parkinsonism improved significantly as assessed by the part "motor examination" of the Unified Parkinson's Disease Rating Scale (UPDRS). However, the total error scores of the Farnsworth-Munsell 100-Hue test before and after amantadine sulphate infusions were unchanged [before therapy, 94.53 (SD = 52.09); after therapy, 99.5 (SD = 58.81)]. From these results, it can be concluded that the pathophysiology of dopaminergic pathways in the visual system differs from that of the basal ganglia.

Aged↗