Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
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Alanine↗
Biomedical subjects
T Müller
Publications and source records attributed to T Müller.
The mechanism of action of cantharidin in smooth muscle.
1. The aim of this study was to investigate the mechanism(s) of the vasoconstrictor effect of cantharidin in bovine preparations. 2. Catalytic subunits of protein phosphatase type 1 (PP 1) and type 2A (PP 2A) were immunologically identified in coronary arteries, isolated smooth muscle cells and ventricular myocardium. 3. The mRNAs coding for catalytic subunits of PP 1alpha, PP 1beta and PP 2Aalpha were identified by hybridization with specific cDNA-probes in total RNA from coronary arteries, isolated smooth muscle cells and ventricles. 4. The activities of catalytic subunits of PP 1 and PP 2A separated by column chromatography from coronary arteries, isolated smooth muscle cells and ventricles were inhibited by cantharidin in a concentration-dependent manner. 5. Cantharidin increased the phosphorylation state of smooth muscle proteins including the regulatory light chains of myosin in 32P-labelled intact smooth muscle cells in a concentration-dependent manner. 6. Cantharidin did not affect cytosolic calcium concentrations in aortic smooth muscle cells. 7. It is suggested that cantharidin contracts smooth muscle preparations by increasing the phosphorylation state of regulatory proteins due to inhibition of phosphatase activities. Thus, cantharidin might be a useful tool to study the function of phosphatases in smooth muscle.
Animals↗
Heterogeneity of plant-associated streptococci as characterized by phenotypic features and restriction analysis of PCR-amplified 16S rDNA.
Thirty-five strains of streptococci isolated from forage grasses were examined by restriction analysis of PCR-amplified 16S rDNA. Using a set of seven endonucleases, five 16S rDNA genotypes were obtained. The isolates could be identified as belonging to the species Enterococcus faecium, Ent. mundtii, Ent. faecalis, Ent. casseliflavus and Lactococcus lactis ssp. lactis, respectively. To assign the isolates to one of these species, digestion with the endonuclease HinfI was sufficient. Data obtained from whole-cell protein analysis were in accordance with the species identification. Additionally, three of the five species found were subdivided into two related subgroups. Both methods are suitable for a rapid and unequivocal identification of plant-associated streptococci. The phenotypic characters showed a high diversity and were in some cases contrary to the expected features usually given in genus and species descriptions. The results demonstrated the close relatedness of the determined species in contrast to their high phenotypic heterogeneity.
Bacterial Typing Techniques↗
Novel pluripotential neural progenitor lines exhibiting rapid controlled differentiation to neurotransmitter receptor-expressing neurons and glia.
The immortalization of progenitor cells from embryonic murine hippocampus using oncogene-carrying retroviral vectors is described. Use of a vector encoding the oncogene v-myc results in lines of nestin-positive progenitor cells. Limited differentiation ensues if the cells are cultured in the presence of dibutyryl cyclic adenosine monophosphate. In contrast, use of a vector in which the extracellular portion of the epidermal growth factor (EGF) receptor is fused to the neu tyrosine kinase generates lines of pluripotential nestin-positive progenitor cells, which differentiate upon withdrawal of EGF into neurons and glia. Differentiated neurons expressing action potentials and neurotransmitter receptors make up a high proportion of the cells. These cell lines are useful tools to investigate the characteristics of differentiating neurons and glia, as well as to screen neuroactive drugs. This work has been reported in preliminary form as an abstract (1996 Society for Neuroscience Abstract, #606.20, p. 1537).
Action Potentials↗
Successful abdominal delivery in a woman with sonographic diagnosis of diffuse cavernous hemangioma of the uterus.
Diffuse hemangioma of the pregnant uterus is a serious lesion. We report the first case of a successful cesarean section at term following expectant management of pregnancy in a patient with presumed isolated diffuse cavernous hemangioma of the uterus and protein S deficiency. The sonographic diagnosis and clinical management of this condition is described. The presented successful pregnancy underlines that, under close surveillance, consideration should be given to a conservative approach to this sonographic finding during pregnancy, as even an abdominal delivery does not imply hysterectomy inevitably.
Adult↗
[The incidence and significance of unusual neurologic signs. A clinical study].
Little is known about extrinsic-intrinsic reflexes, especially the prototype combinative extensor hallucis response, which become apparent if proprioceptive and exteroceptive afferents of the concerning muscles are stimulated simultaneously as well as successively. With reference to this phenomenon, data from 604 patients were evaluated under neurological aspects. With the exception of the combinative reflex of the peroneal muscles, the occurrence of other combinative reflexes (of tibial posterior, anterior and extensor hallucis muscles) was of clinical relevance. All these characteristics, in the same way as Tramer's reflex and unilateral tibialis posterior reflex, correlated very well statistically with typical symptoms of an upper motor neurone syndrome. In this context the extensor hallucis combinative response is the most important one. This particular sign occurred in a systematically examined population of patients twice as often as Babinski's sign and was the single reflex anomaly in 7 per cent of 200 systematically examined cases. A double-sided manifestation, which could be seen exclusively as physiological, appeared in less than 2 per cent of 604 cases. In respect of the occurrence of combinative responses, patients belonging to different diagnostic groups, infants as well as adults, did not have statistically the same basic probability with regard to the examined neurological signs. Hence, an examination of healthy persons would not yield essential evidence. In our opinion such combinative reflexes and the other symptoms mentioned may be useful in detecting latent upper motor neuron lesion or may be helpful in doubtful cases. Whether or not the phenomenon of a combinative reflex really represents part of the latent pathognomonic flexor withdrawal reflex, cannot be decided with our clinical methods.
Adolescent↗
Idiopathic copper toxicosis.
Liver diseases of infancy and childhood are generally rare and within the spectrum of these disorders, only a few subtypes are related to abnormal hepatic copper accumulation. Idiopathic copper toxicosis has been defined as such a subtype; although this disease is characterized by distinct clinical and pathologic features, its exact etiology is still controversial. On the basis of a review of the literature, supplemented by our own observations of 138 cases endemic to western Austria, we hypothesize that idiopathic copper toxicosis is caused by a synergy of an autosomal-recessive inherited defect in copper metabolism and excess dietary copper. Increased awareness of the disease should enable early diagnosis and lead to successful treatment, thereby improving the overall poor prognosis of affected patients.
Child, Preschool↗
The cellular stress response induced by aqueous extracts of cigarette smoke is critically dependent on the intracellular glutathione concentration.
Mainstream cigarette smoke (CS) trapped in phosphate-buffered saline solutions (smoke-bubbled PBS) has been shown to induce a strong stress response in cultured cells. This is reflected, for example, by the expression of stress genes such as c-fos and haem oxygenase, a transient decrease in the translation efficiency and the induction of cell cycle arrest. In these studies, peroxynitrite, the reaction product of nitric oxide (NO) and superoxide (O2-.), was identified as an active principle formed by CS in aqueous solutions. In the present study, we show that the CS-induced stress response is critically dependent on the intracellular glutathione (GSH) content which itself becomes diminished in cells exposed to smoke-bubbled PBS. Investigations using c-fos expression as a measure for cellular stress revealed a direct correlation between the smoke-bubbled PBS concentration necessary for stress-dependent c-fos expression and the intracellular GSH concentration observed in different cell lines. Correspondingly, 3T3 fibroblasts artificially depleted of GSH by pretreatment with buthionine-sulphoximine (BSO), an inhibitor of GSH synthesis, require significantly lower amounts of smoke-bubbled PBS to obtain a detectable c-fos expression, whereas, supplementation of the medium with N-acetyl-cysteine is an efficient treatment for the inhibition of a CS-induced c-fos response. We also show that the smoke-bubbled PBS-dependent loss of intracellular GSH is mainly attributable to the aldehyde fraction of CS, although these aldehydes by themselves cannot induce c-fos in these cells. The smoke-bubbled PBS-dependent c-fos response can, however, be mimicked when peroxynitrite and CS-related aldehydes, at the concentrations calculated to appear in smoke-bubbled PBS, are used in combination for cell exposure. Taken together, these results suggest that in cells exposed to aqueous extracts of CS, smoke-related aldehydes decrease the intracellular GSH content significantly, allowing peroxynitrite to interfere with specific target molecules resulting in the stress-specific expression of c-fos.
3T3 Cells↗
High-frequency electric field trapping of individual human spermatozoa.
We present a new touch-free technique for trapping, positioning and selecting human spermatozoa. This can be done in free solution (culture medium) by high-frequency electric fields. Ultramicroelectrodes fabricated by photo- and electron-beam lithography on quartz and glass substrates were used to create field cages or long field channels. If the conductivity of the external salt solution is higher than the average value of sperm cell conductivity, negative polarization and negative dielectrophoresis occur. As a result, the induced cell polarization leads to forces repelling spermatozoa from the electrodes towards the field minimum. Using four planar electrodes a field funnel can be formed in which an individual spermatozoon is retarded while swimming. The same can be done more effectively in three-dimensional cages created by an octopole electrode system. In these systems, rapidly swimming spermatozoa could be trapped for several seconds but some spermatozoa stop moving if exposed to field strengths of more than 500 V/cm at frequencies in the MHz range. However, in stripwise and interdigitated electrodes, rapidly swimming sperm cells could be very well positioned in front of a break-electrode by a combination of electric field trapping and field induced laminar fluid streaming. This technique can be applied to bring individual spermatozoa to a defined position for characterization followed by sampling with capillaries.
Animals↗
Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease.
INTRODUCTION: Several lines of evidence suggest that neuroimmune mechanisms may also be involved in neurodegeneration in Parkinson's disease (PD). The potential role of cytokines such as interleukin 6 (IL-6), in the interaction between neurons and immune system has been emphasized by recent findings. IL-6 induces acute phase protein synthesis, differentiation of neuronal cells and improves catecholaminergic and cholinergic cell survival in the brain. SUBJECTS AND METHODS: We determined levels of IL-6 in cerebrospinal fluid (CSF) of untreated parkinsonian patients and age- and sex-matched controls. Intensity of disease was evaluated by the Unified Parkinson's Disease Rating scale. RESULTS: Significantly elevated levels of IL-6 were found in the CSF of parkinsonian patients. Moreover a significant inverse correlation between severity of PD and IL-6 CSF levels appeared. DISCUSSION: Elevated IL-6 levels in the CSF of untreated parkinsonian patients may reflect the original condition in the course of disease. We speculate that an endogenous upregulation of IL-6 synthesis occurs in order to regenerate lesioned neurons probably at an early phase of the degenerative process in PD.
Adult↗
Central pontine myelinolysis causes bilateral loss of deep sensitivity and pseudochoreoathetosis.
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Adult↗
[123I]beta-CIT SPECT visualizes dopamine transporter loss in de novo parkinsonian patients.
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the basal ganglia, which may be visualized by single photon emission computed tomography (SPECT) in combination with the cocaine analog methyl-3-beta-(4-beta[123I]iodophenyl)tropane-2beta-carboxylate ([123I]beta-CIT). The aim of our study was to correlate findings of SPECT with clinical data of 34 previously untreated, idiopathic parkinsonian patients [age: 59.58+/-10.03 (mean+/-SD) years; Hoehn and Yahr Scale (HYS) mean range: 1.97+/-0.83, ranges I-III; Unified PD Rating Scale 3.0 (UPDRS, 30.64+/-18.68) and 15 healthy controls (age 47.93+/-10.47 years). SPECT scans were performed with a single-head gamma-camera 24 h after intravenous injection of [123I]beta-CIT. Comparison of the striatum/cerebellum (S/C) ratio of [123I]beta-CIT uptake of controls and parkinsonian subjects, subdivided according to their HYS range, was significant. No influence of age or sex was observed. Significant correlations were found between scores of the HYS, UPDRS parts I-III, part II, part III, and the S/C ratio of [123I]-CIT uptake. Moreover, SPECT with the radiotracer [123I]beta-CIT revealed side-to-side differences in parkinsonian patients and significant associations to contralateral clinical extrapyramidal symptomatology. Our data show that SPECT with [123I]beta-CIT is a valuable tool for estimating disease severity in PD.
Adult↗
Elevated plasma levels of homocysteine in Parkinson's disease.
Significantly elevated plasma levels of homocysteine, but not cysteine and cysteinylglycine, were found in treated parkinsonian patients compared to controls. Elevated levels of homocysteine may be either caused by an unknown endogenous metabolic disturbance or by antiparkinsonian treatment, because no association to severity or duration of disease was found. Based on the results of this study one may speculate that homocysteine may be an independent risk factor for vascular disease in Parkinson's disease.
Aged↗
High prevalence of parkinsonism after occupational exposure to lead-sulfate batteries.
Seven of nine postal workers exposed to lead-sulfate batteries over a period of up to 30 years developed parkinsonian symptoms. One of the remaining two showed left-hand bradykinesia and one was not available for examination. The high prevalence and cause of parkinsonism in these patients remains unexplained. Lead intoxication may play a role in the occurrence of parkinsonian symptoms, but involvement of sulfate and other sulfur compounds must also be considered.
Antiparkinson Agents↗
POU transcription factors control expression of CNS stem cell-specific genes.
Multipotential stem cells throughout the developing central nervous system have common properties. Among these is expression of the intermediate filament protein nestin and the brain fatty acid binding protein (B-FABP). To determine if common mechanisms control transcription in CNS stem cells, the regulatory elements of these two genes were mapped in transgenic mice. A 257 basepair enhancer of the rat nestin gene is sufficient for expression throughout the embryonic neuroepithelium. This enhancer contains two sites bound by the class III POU proteins Brn-1, Brn-2, Brn-4, and Tst-1. Only one of the two POU sites is required for CNS expression. An adjacent hormone response element is necessary for expression in the dorsal midbrain and forebrain. The regulatory sites of the B-FABP gene are strikingly similar to those of the nestin gene. A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2. This site is essential for expression in most of the CNS. In addition, a hormone response element is necessary for forebrain expression. Both the nestin and B-FABP genes therefore depend on POU binding sites for general CNS expression, with hormone response elements additionally required for activity in the anterior CNS. These data indicate that regulation by POU proteins and hormone receptors is a general mechanism for CNS stem cell-specific transcription.
Animals↗
Methylene blue supravital staining: an evaluation of its applicability to the mammalian brain and pineal gland.
Methylene blue supravital staining of mammalian brain reveals typical staining patterns in different brain regions. Within the cerebellum of the mouse, the dye showed a peculiar affinity for the somata and the axons of Purkinje cells. Additionally, large polymorphic neurons characterized by long descending axons were detected within the granular layer and the white matter. These cells might represent another type of projection neuron. In the stratum pyramidale and stratum oriens of the murine hippocampus, a subpopulation of non-pyramidal cells, i.e. intrinsic interneurons, were selectively stained. Additionally, a labelling of perineuronal nets of extracellular matrix covering single cells could be achieved; this phenomenon might be due to the occurrence of strong anionic residues which attract the cationic dye. Therefore, perineuronal nets might also trap other cations and play an important role in the control of cell excitability. The electron microscopic investigation revealed drop-like dye accumulations within the cytoplasm and a staining of material at the site of the plasma membrane. Throughout the pineal gland, a network of a subpopulation of polymorphic cells with manifold long processes could be visualized. Syncytial connections of cells seemed to occur. The oxygen-dependent selective staining is probably functionally connected with the generation of oxygen radicals and subsequent oxidative stress for the cells. This reaction indicates a certain vulnerability to hypoxia; therefore, the intracellular dye-uptake might be interpreted as an early sign of metabolic disturbance.
Animals↗
The innervation of taste buds in the soft palate and circumvallate papilla of the rat as revealed by the zinc iodide-osmium tetroxide technique.
The taste buds in the soft palate and the circumvallate papillae of the rat were investigated by the zinc iodide-osmium tetroxide technique. In addition, electron micrographs of taste buds stained with this method were presented for the first time. Differences in taste bud structures were found between the examined regions. The taste buds of the soft palate showed a complicated plexus of intragemmal nerve fibers. Some fibers exhibited terminal polymorphic swellings. Single branches could be traced close to the space of the taste pore. In the soft palate, the taste bud cells remained unstained, whereas in the circumvallate papillae of the tongue, a subpopulation of taste bud cells could be selectively stained and the intragemmal nerve fibers were characterized by large varicosities. The morphological dissimilarities between the taste buds of the investigated regions might be explained by their functional characteristics, or possibly their varying affinities to the taste qualities. Electron microscopic investigation of the stained circumvallate papillae revealed that the electron-dense reaction product had primarily accumulated in a subpopulation of light cells. Dark cells exhibited only a slight labelling. In detail, the precipitate was found loosely distributed in the cytoplasm as well as the nuclei of the cells, and particularly concentrated at the membranes of light vacuoles, this probably being profiles of dilated endoplasmic reticulum. A few roundish accumulations of precipitate were seen in the cytoplasm of taste bud cells, which showed no intensive light microscopic staining. Labelled material was also found within the taste pores outside the apical processes of the cells. The present findings indicate that the zinc iodide-osmium tetroxide technique is applicable to neuroanatomical studies of taste buds.
Animals↗
Pseudorabies in the European wild boar from eastern Germany.
Sera collected from European wild boar (Sus scrofa) shot in Eastern Germany between January 1991 and December 1994 were tested for antibodies to pseudorabies virus (PRV). Of 3,143 sera tested, 281 (8.9%) and 13 (0.4%) were positive and suspect in an enzyme-linked immunosorbent assay (ELISA), respectively. The specificity of the reactions was confirmed by detection of neutralizing antibodies in 220 sera (74.8%) and by immunoblotting. Analysis of host age and sex of the animals, temporal and spatial factors showed significantly higher seroprevalences in older animals than in younger individuals, but no differences between males and females. Pseudorabies virus infections have been endemic in this wild boar population for several years and the extreme eastern part of the study area had significantly higher seroprevalences (< or = 22%) than other areas. In the area covered by this study, pseudorabies virus was eradicated in the domestic animal populations in 1985. Thus, the infections in the wild boar population appear to be endemic and persist completely separately and without affecting the domestic pig population.
Age Factors↗