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91.
Monique Albersen Marjolein Bosma Judith J. M. Jans Floris C. Hofstede Peter M. van Hasselt Monique G. M. de Sain-van der Velden Gepke Visser Nanda M. Verhoeven-Duif 《PloS one》2015,10(3)
Background
Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce.Materials and Methods
B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples could not be obtained from healthy children. The influence of sex, age, epilepsy and treatment with anti-epileptic drugs, were investigated.Results
The B6 vitamer composition of plasma (pyridoxal phosphate (PLP) > pyridoxic acid > pyridoxal (PL)) differed from that of CSF (PL > PLP > pyridoxic acid > pyridoxamine). Strong correlations were found for B6 vitamers in and between plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased concentrations of PL and PLP in CSF.Conclusion
We provide concentrations of all B6 vitamers in plasma and CSF of children with intellectual disability (±epilepsy), which can be used in the investigation of known and novel disorders associated with vitamin B6 metabolism as well as in monitoring of the biochemical effects of treatment with vitamin B6. 相似文献92.
Michael Schneider Valéa Schumacher Timo Lischke Karsten Lücke Catherine Meyer-Schwesinger Joachim Velden Friedrich Koch-Nolte Hans-Willi Mittrücker 《PloS one》2015,10(5)
The enzyme CD38 is expressed on a variety of hematopoietic and non-hematopoietic cells and is involved in diverse processes such as generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Here, we show that under homeostatic conditions CD38 is highly expressed on immune cells of the colon mucosa of C57BL/6 mice. Myeloid cells recruited to this tissue upon inflammation also express enhanced levels of CD38. To determine the role of CD38 in intestinal inflammation, we applied the dextran sulfate sodium (DSS) colitis model. Whereas wild-type mice developed severe colitis, CD38-/- mice had only mild disease following DSS-treatment. Histologic examination of the colon mucosa revealed pronounced inflammatory damage with dense infiltrates containing numerous granulocytes and macrophages in wild-type animals, while these findings were significantly attenuated in CD38-/- mice. Despite attenuated histological findings, the mRNA expression of inflammatory cytokines and chemokines was only marginally lower in the colons of CD38-/- mice as compared to wild-type mice. In conclusion, our results identify a function for CD38 in the control of inflammatory processes in the colon. 相似文献
93.
The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial
design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for
their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment
efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis
it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase
in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform
appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected
for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by
an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion
(D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr
2 values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion
kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained
with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful
for once-a-day intramuscular administration of ketorolac tromethamine.
Published: February 23, 2007 相似文献
94.
Classical quantitative genetics has applied linear modeling to the problem of mapping genotypic to phenotypic variation. Much of this theory was developed prior to the availability of molecular biology. The current understanding of the mechanisms of gene expression indicates the importance of nonlinear effects resulting from gene interactions. We provide a bridge between genetics and gene network theories by relating key concepts from quantitative genetics to the parameters, variables, and performance functions of genetic networks. We illustrate this methodology by simulating the genetic switch controlling galactose metabolism in yeast and its response to selection for a population of individuals. Results indicate that genes have heterogeneous contributions to phenotypes and that additive and nonadditive effects are context dependent. Early cycles of selection suggest strong additive effects attributed to some genes. Later cycles suggest the presence of strong context-dependent nonadditive effects that are conditional on the outcomes of earlier selection cycles. A single favorable allele cannot be consistently identified for most loci. These results highlight the complications that can arise with the presence of nonlinear effects associated with genes acting in networks when selection is conducted on a population of individuals segregating for the genes contributing to the network. 相似文献
95.
96.
97.
Mark J. de Lange Lubna Razzaq Mieke Versluis Sven Verlinde Mehmet Dogrus?z Stefan B?hringer Marina Marinkovic Gregorius P. M. Luyten Rob J. W. de Keizer Frank R. de Gruijl Martine J. Jager Pieter A. van der Velden 《PloS one》2015,10(9)
Uveal melanomas (UM) originate from melanocytes in the interior wall of the eye, namely from the iris, ciliary body and the choroid with marked differences in light exposure (from dark anterior to illuminated posterior). In contrast to UV radiation, focused or converging visible light readily reaches the retina and can damage DNA which possibly contributes to UM development. In this report choroidal, ciliochoroidal and iridociliary melanomas were analyzed for GNAQ and GNA11 mutations which were subsequently correlated to the location of tumor origin. Hotspot mutations in GNAQ and GNA11 can be divided in A>T and in A>C mutation signatures. The GNAQ A626C mutation (Q209P) was almost exclusively observed in choroidal melanomas from the illuminated posterior side. On the other hand, ciliochoroidal UM from the dark anterior side with mostly A>T mutations were clearly associated with light-colored eyes. Combined these data suggest a light and a pigment dependent etiology in UM development. 相似文献
98.
Ivan Stojanović Thomas J.G. van der Velden Heleen W. Mulder Richard B.M. Schasfoort Leon W.M.M. Terstappen 《Analytical biochemistry》2015
Surface plasmon resonance imaging (SPRi) is most frequently used for the label-free measurement of biomolecular interactions. Here we explore the potential of SPRi to measure antibody production of individual hybridoma cells. As a model system, cells from a hybridoma, producing monoclonal antibodies recognizing epithelial cell adhesion molecule (EpCAM), were used. Recombinant human EpCAM protein was immobilized on an SPR sensor and hybridoma cells were introduced into an IBIS MX96 SPR imager and the SPRi response was followed for 10 h. SPRi responses were detected on the spots of the sensor only where ligands of the produced antibody were present. By measuring the SPRi signals on individual cells the antibody production of the individual cells was measured and production rates were calculated. For 53 single EpCAM hybridoma cells the production ranged from 0.16 to 11.95 pg (mean 2.96 pg per cell, SD 2.51) over a period of 10 h. Antibody excretion per cell per hour ranged from 0.02 to 1.19 pg (mean 0.30, SD 0.25). Here we demonstrate for the first time that antibody production of individual cells can be measured and quantified by SPRi, opening a new avenue for measuring excretion products of individual cells. 相似文献
99.
Background
Individuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis.Methodology
We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals.Principal Findings
Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT 158 genotype.Conclusions
These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals. 相似文献100.
A. Güçlü T. Germans E. R. Witjas-Paalberends G. J. M. Stienen W. P. Brouwer H. J. Harms J. T. Marcus A. B. A. Vonk W. Stooker A. Yilmaz P. Klein J. M. ten Berg J. Kluin F. W. Asselbergs A. A. Lammertsma P. Knaapen A. C. van Rossum J. van der Velden 《Netherlands heart journal》2013,21(12):567-571