Search

BACKGROUND: During pregnancy, the placenta may become exposed to micro-organisms, such as viruses, which may pose a substantial threat to the embryo/fetus well-being. Recent insight into the immunological capabilities of the trophoblast suggests that the placenta may function as an active barrier by recognizing and responding to pathogens through Toll-like receptors (TLRs). METHODS: The objective of this study was to determine whether the engagement of TLR-3 with viral dsRNA by first-trimester trophoblast could induce the production of factors necessary to generate an antiviral response. Therefore, trophoblast cells were exposed to the TLR-3 agonist, Poly(I : C). RESULTS: We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon β (IFNβ) and secretory leukocyte protease inhibitor (SLPI), as well as the intracellular factors 2′,5′-oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). This response is TLR-3 specific because the TLR-4 ligand, lipopolysaccharide (LPS), had no effect on the production of these antimicrobial factors. Furthermore, we describe a positive feedback mechanism in which IFNβ enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G. CONCLUSIONS: These findings suggest that trophoblast cells are able to recognize and specifically respond to viral products in a highly regulated fashion and that the placenta may be pivotal in the control of viral infections at the maternal–fetal interface. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Weight gain is a frequently observed adverse event in the treatment with atypical antipsychotics that significantly affects the patients' physical health and treatment compliance. METHODS: We report on a treatment-resistant schizophrenic patient who received an add-on treatment with the low-affinity NMDA antagonist memantine because of cognitive disturbances. RESULTS: During this treatment we observed a marked decrease of clozapine-induced weight gain. The causal relationship to memantine could be demonstrated using an on-off-on design with a significant increase of weight after discontinuation and again a substantial weight loss after re-exposition with memantine. Beside weight, also negative symptoms improved. DISCUSSION: Prospective controlled trials evaluating the safety and possible positive effects of memantine on antipsychotic induced weight gain are needed. [ABSTRACT FROM AUTHOR]

The purpose of this work is to investigate the correlation between magnetism and crystallographic structures of Mn2NiGa thin films grown by molecular beam epitaxy on GaAs(1 1 1) and GaAs(0 0 1) surfaces. The films present themselves with thermoelastic martensitic transformations upon cooling, and heating with high-temperature leads to austenite structures exhibiting a preferable (1 1 0) texture. X-ray diffraction measurements performed as a function of temperature reveal three different types of domain variants in the films within a large interval of temperatures. The austenite structures with lattice parameters ranging from 0.574 nm to 0.601 nm undergo volume conserving structural transitions to martensite with a c/a ratio of 1.2. The coexistence of variants with different domain configurations is induced on each GaAs substrate. Although the Curie temperatures (~360 K) are similar for films grown on GaAs(1 1 1) and GaAs (0 0 1) substrates, their saturation magnetizations are respectively 18 kA m−1 and 8 kA m−1 at room temperature and exhibit quite different magnetic irreversibility behaviors. Our results indicate that a multiplicity of possible equivalent variant domains on the GaAs surfaces makes it difficult to stabilize epitaxial films on these substrates. [ABSTRACT FROM AUTHOR]

The textural patterns in the lung parenchyma, as visible on computed tomography (CT) scans, are essential to make a correct diagnosis in interstitial lung disease. We developed one automatic and two interactive protocols for classification of normal and seven types of abnormal lung textures. Lungs were segmented and subdivided into volumes of interest (VOIs) with homogeneous texture using a clustering approach. In the automatic protocol, VOIs were classified automatically by an extra-trees classifier that was trained using annotations of VOIs from other CT scans. In the interactive protocols, an observer iteratively trained an extra-trees classifier to distinguish the different textures, by correcting mistakes the classifier makes in a slice-by-slice manner. The difference between the two interactive methods was whether or not training data from previously annotated scans was used in classification of the first slice. The protocols were compared in terms of the percentages of VOIs that observers needed to relabel. Validation experiments were carried out using software that simulated observer behavior. In the automatic classification protocol, observers needed to relabel on average 58% of the VOIs. During interactive annotation without the use of previous training data, the average percentage of relabeled VOIs decreased from 64% for the first slice to 13% for the second half of the scan. Overall, 21% of the VOIs were relabeled. When previous training data was available, the average overall percentage of VOIs requiring relabeling was 20%, decreasing from 56% in the first slice to 13% in the second half of the scan. [ABSTRACT FROM AUTHOR]

Dramatic tissue variation in mitochondrial heteroplasmy has been found to exist in patients with sporadic mitochondrial DNA (mtDNA) mutations. Despite high abundance in mature skeletal muscle, levels of the causative mutation are low or undetectable in satellite cells. The activation of these typically quiescent mitotic cells and subsequent shifting of wild-type mtDNA templates to mature muscle have been proposed as a means of restoring a more normal mitochondrial genotype and function in these patients. Because resistance exercise is known to serve as a stimulus for satellite cell induction within active skeletal muscle, this study sought to assess the therapeutic potential of resistance training in eight patients with single, large-scale mtDNA deletions by assessing: physiological determinants of peak muscle strength and oxidative capacity and muscle biopsy-derived measures of damage, mtDNA mutation load, level of oxidative impairment and satellite cell numbers. Our results show that 12 weeks of progressive overload leg resistance training led to: (i) increased muscle strength; (ii) myofibre damage and regeneration; (iii) increased proportion of neural cell adhesion molecule (NCAM)-positive satellite cells; (iv) improved muscle oxidative capacity. Taken together, we believe these findings support the hypothesis of resistance exercise-induced mitochondrial gene-shifting in muscle containing satellite cells which have low or absent levels of deleted mtDNA. Further investigation is warranted to refine parameters of the exercise training protocol in order to maximize the training effect on mitochondrial genotype and treatment potential for patients with selected, sporadic mutations of mtDNA in skeletal muscle. [ABSTRACT FROM AUTHOR]

The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [18f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower α band (8.5–10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging. Hum. Brain Mapping 21:257–270, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

: Background The effects of xenon on regional cerebral blood flow (rCBF) are controversial. Moreover, the precise sites of action at which xenon exerts its effects in the human brain remain to be established. : Methods rCBF was sequentially assessed by H215O positron emission tomography in six volunteers. rCBF was determined at baseline and during general anaesthesia induced with propofol and maintained with one minimum alveolar concentration xenon. rCBF measurements were started after the calculated plasma concentration of propofol had decreased to subanaesthetic levels (<1.0 µg ml−1). Changes in rCBF were calculated for 13 cerebral volumes of interest by measurement of a semi-quantitative perfusion index (PI). In addition, voxel-wise changes in rCBF were analysed using statistical parametric mapping. : Results Xenon had only minor effects on PI in grey matter volumes of interest. In contrast, PI was increased in white matter [from 1.01 (0.11) to 1.24 (0.15) kcnt ml−1 MBq−1, P=0.05, mean (sd)]. Voxel-based analysis showed an increase of rCBF in white matter and a relative decrease of rCBF during xenon anaesthesia in distinct grey matter regions, particularly the orbito- and mesiofrontal cortex, cingulate gyrus, thalamus, hippocampus and bilateral cerebellum (P<0.05 corrected). When correlating PI with cerebral metabolic rate of glucose (previously obtained in another group of six volunteers using 18F-fluorodeoxyglucose as tracer), the flow–metabolism coupling was preserved during xenon anaesthesia. : Conclusions Xenon exerted distinct regional effects on CBF: relative decreases in several cortical, subcortical, and cerebellar areas were accompanied by an increase in white matter. Flow–metabolism coupling was not impaired during xenon anaesthesia. [ABSTRACT FROM AUTHOR]

Mutations in nuclear genes involved in mitochondrial DNA (mtDNA) maintenance cause a wide range of clinical phenotypes associated with the secondary accumulation of multiple mtDNA deletions in affected tissues. The majority of families with autosomal dominant progressive external ophthalmoplegia (PEO) harbour mutations in genes encoding one of three well-characterized proteins—polγ, Twinkle or Ant 1. Here we show that a heterozygous mis-sense mutation in OPA1 leads to multiple mtDNA deletions in skeletal muscle and a mosaic defect of cytochrome c oxidase (COX). The disorder presented with visual failure and optic atrophy in childhood, followed by PEO, ataxia, deafness and a sensory-motor neuropathy in adult life. COX-deficient skeletal muscle fibres contained supra-threshold levels of multiple mtDNA deletions, and genetic linkage, sequencing and expression analysis excluded POLG1, PEO1 and SLC25A4, the gene encoding Ant 1, as the cause. This demonstrates the importance of OPA1 in mtDNA maintenance, and implicates OPA1 in diseases associated with secondary defects of mtDNA. [ABSTRACT FROM AUTHOR]