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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 217 records · Page 12Linked to original sources
PubMed1999

Generators of brain electrical activity in patients with Wilson's disease.

Electroencephalographic (EEG) generators were investigated in 13 patients suffering from hepatolenticular degeneration with and without neurological symptoms and in 13 healthy subjects for comparison by the use of FFT approximation. Quantitative assessment of motor deficits and psychiatric disturbances was correlated with EEG features. We found mainly an increase in delta activity, a decrease in alpha activity combined with a more posterior localisation of the EEG generators in the delta band and a more anterior one in the alpha band in patients compared with healthy controls. The localisation of the EEG generators in the patients with clinical apparent neurological symptoms were in all frequency bands more superficial compared with controls and patients without neurological symptoms. With longer duration of the disease, the lower the premorbid intelligence the more posterior was the delta EEG generator localised. Although the alpha EEG generator was more anteriorly localised with longer duration of the disease and more severe cognitive deficits, it was more superficial with more pronounced psychiatric symptoms, more severe cognitive deficits, lower premorbid intelligence and more pronounced motor disabilities. With more pronounced psychiatric symptoms and cognitive deficits, the beta EEG generator was more anteriorly localised. The present study demonstrated that a significant deviant EEG pattern exists between patients with and without clinical neurological symptoms and that stage-dependent alterations in psychiatric symptoms and cognitive ability are reflected on the EEG.

Adult↗
PubMed1999

Serum levels of neuron-specific enolase and s-100 protein after single tonic-clonic seizures.

Serum neuron-specific enolase (s-NSE) and s-100 protein (s-100) are sensitive markers of various brain diseases. We investigated both of these markers in nine patients within 5 min, 6 h, 12 h, and 48 h after a single tonic-clonic seizure. The mean peak s-NSE level was significantly higher after 5 min (11.97 +/- 8.56 microg/l) and 48 h (10.31 +/- 8.92 microg/l, P < 0.05) than the levels of seizure-free, age-matched controls. Five patients had increased s-NSE levels regarding the upper limit of normal as mean + 3 SD. s-100 was not detected either in controls or epileptic patients. These data indicate that s-NSE in contrast to s-100 may be an in vivo marker after generalized seizures in some patients.

Adult↗
PubMed1999

The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors.

Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.

Animals↗
PubMed1999

Analysis of the parkin deletion in sporadic and familial Parkinson's disease. Short communication.

Recently a mutation in the parking gene has been identified as the cause for an autosomal-recessively inherited form of early onset Parkinson's disease (EOPD). The disease causing minimal deletion has been defined as a homozygous exon 4 loss in the parkin gene among Japanese patients. We investigated 140 sporadic and familial EOPD patients of German ancestry for the exon 4 deletion in the parkin gene. None of our patients exhibited a homozygous deletion of exon 4, suggesting a minor role of this mutation for EOPD in Caucasians. Nevertheless a detailed mutation analysis is warranted to explore the overall significance of mutations in the parkin gene in EOPD.

Adult↗
PubMed1999

Familial clustering of infantile cirrhosis in Northern Germany: A clue to the etiology of idiopathic copper toxicosis.

Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet.

Age of Onset↗
PubMed1999

Mycotoxins of Aspergillus fumigatus in pure culture and in native bioaerosols from compost facilities.

Exposure to secondary metabolites of airborne fungi in waste handling facilities is discussed in regard to potential toxic impacts on human health. The relevance of mycotoxins has been intensely studied in connection with contamination of food and feed. Toxic secondary metabolites are expected to be present in airborne spores, but exposure to mycotoxins in bioaerosols has not been studied sufficiently. Aspergillus fumigatus is one of the most frequent species in the air of compost plants. A wide range of secondary metabolites was found in pure cultures of freshly isolated strains of A. fumigatus. Tryptoquivaline, a compound with tremorgenic properties, and trypacidin, for which no toxic properties are described, were found in native bioaerosols in a compost facility. The highly toxic metabolites gliotoxin and verruculogen were not found in the bioaerosols.

Aerosols↗
PubMed1999

An update on safety studies of SAD B19 rabies virus vaccine in target and non-target species.

SAD B19 is an attenuated vaccine virus for oral vaccination of carnivores against rabies. The safety of SAD B19 was investigated in 16 animal species by different routes of administration. During the observation period all animals given the vaccine virus, irrespective of the route of administration, did not show any clinical signs of rabies, with the exception of certain rodent species. In these animals a low residual pathogenicity was observed, however transmission of the vaccine virus to control animals was not demonstrable. No vaccine virus could be detected in the saliva of the six mammal species examined. Furthermore, the genetical stability was shown for SAD B19 through passaging in neural tissue of dogs, foxes and mice. From the results presented here on innocuity and stability, it can be concluded that SAD B19 rabies vaccine is suitable for oral vaccination campaigns for carnivores against rabies.

Administration, Oral↗
PubMed1999

Colour vision abnormalities and movement time in Parkinson's disease.

Visual system dysfunction has been reported in Parkinson's disease (PD). The objective of the present study was to evaluate a putative association of distorted colour vision and delayed initiation and execution of movement in PD. We performed the Farnsworth-Munsell 100-hue test and estimated the total error score in 30 previously untreated parkinsonian patients and 30 age- and sex-matched controls. We then determined slowness in motor readiness and motor programming in the parkinsonian subjects on the same day. Subjects were asked to press a start button and release it after the randomized appearance of a visual stimulus and to move their right index finger to a reaction button as quickly as possible. Reaction time was considered as elapsed time between onset of the stimulus light and release of the start button, movement time was the time period between release of the start button and the pressing of the reaction button. Significant differences appeared between parkinsonian patients' and controls' reaction times (P = 0.007), movement time (P = 0.001) and total error score (P = 2.23E-08). A significant relation (Spearman R = 0.473, P = 0.008) was found between movement time and total error score, but not between reaction time and total error score (Spearman R = 0.259, P = 0.166). We conclude, that visual dysfunction and execution of movement are more influenced by altered dopaminergic neurotransmission in PD in comparison to the initiation of movement.

Adult↗
PubMed1999

Characteristic intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat: morphological details revealed by intravital methylene blue staining and the zinc iodide-osmium tetroxide technique.

Light microscopic observations employing intravital methylene blue staining and impregnation by the zinc iodide-osmium tetroxide technique are presented for intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat snout. Both procedures revealed anatomical details of the intraepidermal nerve fibre plexus in epidermal hillocks often located very close to the mouths of hairs. These nerve fibres appeared to resemble those described in previous immunohistochemical studies as cluster or bush endings. The methylene blue preparations demonstrated the existence of an intensely stained enlargement at the site of the branching point of the nerve fibres which seemed to be functionally related to the development of such nerve fibre plexuses. Due to their close association with hairs, these nerve fibre plexuses are most likely to be mechanoreceptive. Additionally, solitary varicose nerve fibres were found loosely distributed within the epidermis. The visualisation of 2 different morphological types of nerve fibre endings extends the validity of the concept of punctate sensibility into the epidermis. Methylene blue staining appeared to be somewhat superior to the zinc iodide-osmium tetroxide technique. Due to their selectivity for intraepidermal nerve fibres, the methods applied here supplement immunohistochemical procedures in a helpful manner.

Animals↗
PubMed1999

Effects of cannabinoids on dopamine release in the corpus striatum and the nucleus accumbens in vitro.

Cannabinoid receptors are widely distributed in the nuclei of the extrapyramidal motor and mesolimbic reward systems; their exact functions are, however, not known. The aim of the present study was to characterize the effects of cannabinoids on the electrically evoked release of endogenous dopamine in the corpus striatum and the nucleus accumbens. In rat brain slices dopamine release elicited by single electrical pulses was determined by fast cyclic voltammetry. Dopamine release was markedly inhibited by the OP2 opioid receptor agonist U-50488 and the D2/D3 dopamine receptor agonist quinpirole, indicating that our method is suitable for studying presynaptic modulation of dopamine release. In contrast, the CB1/CB2 cannabinoid receptor agonists WIN55212-2 (10(-6) M) and CP55940 (10(-6)-10(-5) M) and the CB1 cannabinoid receptor antagonist SR141716A (10(-6) M) had no effect on the electrically evoked dopamine release in the corpus striatum and the nucleus accumbens. The lack of a presynaptic effect on terminals of nigrostriatal and mesolimbic dopaminergic neurons is in accord with the anatomical distribution of cannabinoid receptors: The perikarya of these neurons in the substantia nigra and the ventral tegmental area do not synthesize mRNA, and hence protein, for CB1 and CB2 cannabinoid receptors. It is therefore unlikely that presynaptic modulation of dopamine release in the corpus striatum and the nucleus accumbens plays a role in the extrapyramidal motor and rewarding effects of cannabinoids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Delayed motor response correlates with striatal degeneration in Parkinson's disease.

OBJECTIVE: Studies on reaction time have suggested a selective deficit of slowness in motor readiness and motor programming in Parkinson's disease (PD). Objective of this study was the putative relation between delayed initiation and execution of movement and the striatal dopamine deficiency in PD. MATERIAL AND METHODS: We investigated 32 idiopathic, previously untreated parkinsonian patients to evaluate dopaminergic nigrostriatal degeneration by single photon emission tomography in combination with the radiotracer [123I]-beta-CIT and performed a simple reaction time paradigm on the same day. RESULTS: Significant relations between the [123I]-beta-CIT-SPECT-ratio striatum/cerebellum and reaction--and movement time appeared. Reaction time and movement time of parkinsonian patients were significantly longer compared to age-matched controls. CONCLUSIONS: We conclude that reaction- and movement-time is related to the dopaminergic nigrostriatal degeneration in untreated parkinsonian subjects.

Adult↗
PubMed1999

Impaired visual function in focal idiopathic dystonia.

Visual dysfunctions have previously been reported in Parkinson's disease and Huntington's chorea. To further characterize the pathophysiology of vision in basal ganglion diseases, we studied visual functions in focal dystonic syndromes. Colour discrimination and visual contrast perception were investigated in 37 patients with focal idiopathic dystonia (ID; 20 spasmodic torticollis, 17 blepharospasm) and in age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100-hue test and stationary contrast targets (Vistech plates). The mean total error score as well as the partial scores for the 'red-green' and the 'blue-yellow' axes in the Farnsworth-Munsell 100-hue test of the patients with ID were significantly elevated as compared to controls (spasmodic torticollis mean total error score 90.9 +/- 67.6, controls: 16.6 +/- 10.2; blepharospasm mean total error score 119.4 +/- 78.6, controls: 22.7 +/- 7.9). Additionally, the spatial contrast sensitivity was impaired in patients as compared to controls. The results indicate that the visual system is affected in ID. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of patients, e.g. in the catecholaminergic pathways.

Adult↗
PubMed1999

Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study.

Dietary omega-3 fatty acids retard coronary atherosclerosis. Previously, we demonstrated that dietary omega-3 fatty acids reduce platelet-derived growth factor (PDGF)-A and PDGF-B mRNA levels in unstimulated, human mononuclear cells (MNCs). In a randomized, investigator-blinded intervention trial, we have now compared the effect of ingestion of 7 g/d omega-3, omega-6, or omega-9 fatty acids for 4 weeks versus no dietary intervention on PDGF-A, PDGF-B, heparin-bound epidermal growth factor (HB-EGF), monocyte chemoattractant protein-1 (MCP-1), and interleukin-10 gene expression in unstimulated MNCs and in monocytes that were adherence-activated ex vivo in a total of 28 volunteers. In unstimulated MNCs, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-10%, 31+/-13%, and 40+/-14%, respectively, after omega-3 fatty acid ingestion, as assessed by quantitative polymerase chain reaction (all P<0.05). In monocytes that were adherence-activated ex vivo for 4 and 20 hours, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-13%, 20+/-15%, and 30+/-8%, respectively (all P<0.05). Interleukin-10 and HB-EGF mRNA steady-state levels were not influenced by omega-3 fatty acid ingestion. Expression of all respective mRNAs in control volunteers or in those ingesting omega-6 or omega-9 fatty acids were not altered. We conclude that human gene expression for PDGF-A, PDGF-B, and MCP-1, factors thought relevant to atherosclerosis, is constitutive, is constant, and can be reduced only by dietary omega-3 fatty acids in unstimulated and adherence-activated monocytes.

Adult↗
PubMed1999

The protein phosphatase inhibitor cantharidin alters vascular endothelial cell permeability.

In this study, we characterized the effects of the protein phosphatases type 1 (PP 1) and type 2A (PP 2A) inhibitor cantharidin in endothelial cells. We identified catalytic subunits of PP 1alpha, PP 2Aalpha, and PP 2Abeta immunologically in bovine aortic endothelial cells. Moreover, we detected mRNAs coding for catalytic subunits of PP 1alpha, PP 1beta, and PP 2Aalpha by hybridization with specific DNA probes in total RNA from these cells. Okadaic acid and cantharidin inhibited the activities of catalytic subunits of PP 1 (okadaic acid, 0.01-1 microM; cantharidin, 1-100 microM) and PP 2A (okadaic acid, 0.1 nM to 1 microM; cantharidin, 0.1-100 microM) separated by column chromatography in a concentration-dependent manner. Moreover, cantharidin (1 microM to 1 mM) increased the phosphorylation state of endothelial proteins including the regulatory light chains of myosin without affecting cytosolic calcium concentrations. Cantharidin (5-100 microM) increased the permeability of cultured endothelial cells in a time- and concentration-dependent manner. We suggest that inhibition of PP 1 and PP 2A activities by cantharidin increases endothelial permeability by enhancing the phosphorylation state of endothelial regulatory proteins. Thus, cantharidin might be a useful tool to study the function of protein phosphatases in endothelial barrier function.

Animals↗
PubMed1999

[Mycotoxins as exposure parameters in bioaerosols of composting sites].

The potential to produce mycotoxins was investigated for freshly isolated strains of airborne fungi. The spectra of metabolites in conidial extracts and culture extracts were compared for some relevant species. Furthermore, their potential to produce mycotoxins on semi-natural media (compost extract agar) supplemented with sucrose, yeast extract, and carboxymethylcellulose in different combinations was investigated. In native bioaerosols in a compost facility (plant 2), tryptoquivaline, a compound with tremorgenic properties, and trypacidin, for which no toxic properties are described, were found. The highly toxic metabolites gliotoxin and verruculogen were not found in the bioaerosols, although they were produced by some strains in pure culture. An inventory of microbial metabolites in addition of fungal propagules has led to a more detailed identification of potential health hazards at the working place. In addition to the pathogenic and allergological relevance, airborne fungi are thus of toxicological concern.

Aerosols↗
PubMed1999

[MVOC of fungi--use as an indicator for exposure level].

The production of microbial volatile organic compounds (MVOC) by fungi derived from biowaste was studied on synthetic agar (YES), compost-extract media (CEA VAR 1-3) and compost. Exposure assessment was carried out in composting facilities and the occurrence of VOC/MVOC was related to the presence of airborne fungi. A number of non-specific MVOC was found at all sampling sites or in each season, some of which showed preferences for certain sampling sites (3-methyl-1-butanol, 3-octanone). They seemed to be correlated with a certain species composition or with microbial activity, and may thus be used to describe a certain state of decomposition. Correlations between single volatiles and certain fungi were found in situ, but these findings did not match with the species-specific volatiles obtained from pure cultures.

Air Pollutants, Occupational↗