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  • 1
    Keywords: brain ; CELLS ; tumor ; Germany ; PATHWAY ; PATHWAYS ; CLASSIFICATION ; SYSTEM ; SYSTEMS ; GENE ; GENES ; TUMORS ; PATIENT ; MECHANISM ; CONTRAST ; mechanisms ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; VARIANTS ; IDENTIFICATION ; LESIONS ; WHITE-MATTER ; SERIES ; pathology ; NEOPLASTIC TRANSFORMATION ; molecular ; VARIANT ; MUTATIONAL ANALYSIS ; ALLELES ; DYSPLASIA ; epilepsy ; focal cortical dysplasia ; FOCAL EPILEPSIES ; GANGLIOGLIOMAS ; glio-neuronal lesion ; GLIONEURONAL TUMORS ; tuberous sclerosis ; TUBEROUS SCLEROSIS COMPLEX
    Abstract: Epilepsy-associated malformations of cortical development (MCDs) comprise a variety of dysplastic and neoplastic lesions of yet undetermined molecular pathology. Histopathologic similarities between MCDs and dysplastic brain lesions in the autosomal inherited neurocutaneous phacomatosis tuberous sclerosis (TSC), which affects the TSC1 and/or TSC2 genes, suggest common pathogenetic mechanisms. Previous studies revealed different alterations of TSC1 and TSC2 in epilepsy-associated malformations and glio-neuronal tumors despite histopathologic similarities. In order to examine current clinico-pathologic classification systems of cortical malformations on the molecular level, we carried out a mutational analysis of TSC1 and TSC2 in a series of surgical specimens obtained from patients with FCD without Taylor type balloon cells (FCDIIa; n = 20), architectural dysplasias (FCDI; n = 15), nodular cortical heterotopias (NCH; It = 4), and heterotopic white matter neurons (WMNH; It = 19). In FCDIIa, abundant genomic polymorphisms were detected in TSC2 (intron 4) but no allelic variants observed in exon 17 of TSCL This allelic distribution pattern is in contrast to findings in FCDI and WMNH but also to those previously reported in FCDIIb (Taylor's balloon cell type). The latter revealed increased frequencies of specific alleles only in TSCL The determination of characteristic molecular genetic alterations in specific epilepsy-associated malformations will support a comprehensive clinico-pathologic classification system and help to identify molecular pathways with potential pathogenetic relevance. Our work is supported by DFG (SFB TRB [AJB], DFG B1 42 1/1-1 [113]), BONFOR, and Deutsche Krebshilfe
    Type of Publication: Journal article published
    PubMed ID: 16042315
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  • 2
    Abstract: The new European chemicals policy for the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) will most probably impose a dramatic increase in the number of animals required for reproductive toxicity testing. For this purpose, the development and validation of alternative methods is urgently needed in order to reduce the use of laboratory animals. The present study describes the inter-laboratory variability and the transferability assessment of an in vitro test able to identify chemical effects during the process of oocyte maturation in a bovine model. The test was developed/optimised within ReProTect, an integrated research project funded by the European Union, joining together 35 partners with complementary expertise in reproductive toxicology. Eight chemicals with well-known toxic properties were tested (benzo[a]pyrene, busulfan, cadmium chloride, cycloheximide, diethylstilbestrol, ketoconazole, methylacetoacetate, mifepristone/RU-486 and DMSO as solvent) on the in vitro maturation (IVM) assay in two well-trained laboratories using the established Standard Operating Procedures. The statistical analysis demonstrated the concordance of results across the laboratories and the reproducibility of the test. We therefore conclude that the IVM test could advance toward the process of validation as alternative in vitro method that, in combination with additional in vitro tests, can become part of an integrated testing strategy in order to predict chemical hazards on mammalian fertility.
    Type of Publication: Journal article published
    PubMed ID: 20156549
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  • 3
    ISSN: 1432-0738
    Keywords: Key words Dithiocarbamates ; Thyroid peroxidase ; Ethylenethiourea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo ethylenebisdithiocarbamates and ETU are toxic to the thyroid gland. Since the molecular target of these compounds is thought to be thyroid peroxidase (TPO) which catalyzes the transfer of iodine to thyroglobulin, we examined the effect of these compounds on peroxidative activity in Chinese hamster ovary (CHO) cells transfected with the human TPO gene. The activity was inhibited by 50 μM ETU, 5 μM ziram and 5 μM zineb, the last-mentioned effect being irreversible in the absence of iodide. Thiram had no effect. By contrast, the iodinating activity of TPO was blocked only by 5 μM ETU and 50 μM zineb but not by the other compounds. The effect on TPO-catalysed iodination could explain the differences in thyrotoxicity of these compounds in vivo.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1106
    Keywords: Premotor cortex ; Arm movement ; Movement direction ; Coordinate system ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of 156 neurons was recorded in the premotor cortex (Weinrich and Wise 1982) and in an adjoining rostral region of area 6 (area 6 DR; Barbas and Pandya 1987) while monkeys made visually-guided arm movements of similar direction within different parts of space. The activity of individual neurons varied most for a given preferred direction of movement within each part of space. These neurons (152/156, 97.4%) were labeled as directional. The spatial orientation of their preferred directions shifted in space to “follow” the rotation of the shoulder joint necessary to bring the arm into the different parts of the work-space. These results suggest that the cortical areas studied represent arm movement direction within a coordinate system rotating with the arm and where signals about the movement direction relate to the motor plan through a simple invariant relationship, that between cell preferred direction and arm orientation in space.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Immune response ; B-hepatitis ; Type 1 (insulin-dependent) diabetes ; vaccination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mIU/ml in normal subjects and 50 mIU/ml in diabetic patients (p〈0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mIU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (〈1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The functional status of dopaminergic nerve terminals has been studied with a method that allows the simultaneous determination of the specific activities of dopamine (DM), tyrosine (Tyr), 3-methoxytyramine (3-MT) and 3,4-dihydroxyphenylacetic acid (DOPAC), after administration of [3H]tyrosine ([3H]Tyr).Combined fluorimetric, mass fragmentographic and radiometric techniques have been used. [3H]Tyrosine was given intraventricularly to unanaesthetized rats and the animals were killed by exposure for 4 s to high energy microwave radiations.The specific activities of 3-MT and DOPAC measured 5 and 20 min after administration of [3H]Tyr, i. e. at time intervals in which the specific activity of DM is rising, are much higher than those their physiological precursor, suggesting that they are generated by more than one DM compartment.This hypothesis seems to be supported by the finding that in animals killed by decapitation instead of microwave radiations the post mortem accumulation of 3-MT occurs to a much smaller extent for the radioactive fraction than for the endogenous one, indicating that 3-MT formed after death may be mainly derived from DM coming from a compartment where this monoamine has been poorly labeled by the radioactive precursor.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— A mass fragmentographic method for the measurement of 3-methoxytyramine, a metabolite of dopamine formed after its neuronal release, is described. This method allows the assay of this dopamine metabolite in the picogram range, thus utilizing only few milligrams of brain areas containing dopaminergic neurons. Moreover, the method is simple and possesses the high specificity intrinsic to mass fragmentography.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The relative rates of accumulation (mg/g fresh weight) of (n-6)tetraenoic and (n-9)trienoic fatty acids in brain and liver of developing rats during essential fatty acid deficiency, show that accumulation of (n-6) acids in brain occurs concomitantly with depletion of the liver stores of polyunsaturated acids, and indicate that considerable accumulation of trienes occurs in the brain, reaching levels (mg/g) even higher than those present in the liver, only after depletion of tetraenes in the liver. The brain thus incorporates very actively long chain polyunsaturated fatty acids both of the (n-6), and of the (n-9) series, when (n-6) compounds are not available any longer.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —Essential fatty acid (EFA) deficiency initiated in rats prior to birth and continued for one year affects brain lipids to an extent which differs in the two sexes. It was found that:(1) Brain weight and lipid content were decreased in deficient conditions, especially in males.(2) Total phospholipids were present in lower concentrations, particularly in the deficient male brain, while the percentage of the major phospholipid classes-ethanolamine phosphoglyceride (EPG), choline phosphoglyceride (CPG) and serine phosphoglyceride (SPG) did not change.(3) Brain EPG, CPG and SPG had distinctive fatty acid patterns differing greatly in polyunsaturation content. PE acids of control females had elevated monoenes and reduced saturates in comparison with control males. This sex difference was lost in the deficient animals.(4) Polyunsaturated fatty acids of EPG, CPG and SPG were markedly changed in animals lacking dietary linoleic acid. Trienoic (C20 and C22) and docosapentaenoic acids were greatly increased, whereas arachidonic, docosatetraenoic and docosahexaenoic acids were much decreased.(5) In spite of the changes in fatty acid composition each of the three phospholipid classes maintained its particular level of unsaturation during EFA deficiency.(6) EPG aldehydes did not change appreciably in deficient conditions.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The protein complex promoting in vitro terminal differentiation of cerebellar granule cells has been isolated from rabbit serum. We designate the complex the neurite outgrowth and adhesion complex (NOAC). The apparent molecular weight, evaluated by gel filtration, is 80–100 kDa. Rat cerebellar granule cells cultured in NOAC exhibit much lower glial cell contamination and survive, in their differentiated state, much longer than in 10% foetal calf serum. While they bind tetanus toxin, express specific antigens such as synapsin l, synaptophisin and A2B5, and release [3H]d-aspartate in a fashion similar to that shown by cells cultured in foetal calf serum, they show a 60% reduction in the total number of kainate binding sites. Excitatory amino acid (EAA)-triggered and depolarization-stimulated calcium influx, measured in the presence of different agonists, is 50–80% lower in NOAC-cultured cells. NOAC cells are resistant to excitotoxic stimuli carried by EAAs or by depolarizing treatments with 50 mM KCI or 6 μM veratridine. The marked resistance of NOAC-cultured neurons to EAAs can be attributed to decreased calcium entry through EAA-coupled and voltage-gated calcium channels and possibly to other, as yet unidentified, phenotypic properties of these cells. These findings demonstrate that rabbit serum contains one or more polypeptide(s) endowed with the properties of promoting in vitro survival and differentiation of rat cerebellar granule cells and of conferring an EAA-resistant phenotype.
    Type of Medium: Electronic Resource
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