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排序方式: 共有141条查询结果,搜索用时 670 毫秒
81.
82.
Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum
Axelsson S Hjorth M Ludvigsson J Casas R 《Diabetic medicine : a journal of the British Diabetic Association》2012,29(10):1272-1278
Diabet. Med. 29, 1272-1278 (2012) ABSTRACT: Aim The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type?1 diabetes, focusing on chemokines and their receptors. Methods Blood samples were collected from 70 children with Type?1 diabetes included in a phase?II clinical trial with GAD-alum. Expression of CC chemokine receptor?5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity. 相似文献
83.
Ewa Soltysinska Bo Hjorth Bentzen Maria Barthmes Helle Hattel A. Brianne Thrush Mary-Ellen Harper Klaus Qvortrup Filip J. Larsen Tomas A. Schiffer Jose Losa-Reyna Julia Straubinger Angelina Kniess Morten B?kgaard Thomsen Andrea Brüggemann Stefanie Fenske Martin Biel Peter Ruth Christian Wahl-Schott Robert Christopher Boushel S?ren-Peter Olesen Robert Lukowski 《PloS one》2014,9(7)
Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK−/− cardiomyocytes. Transmission electron microscopy of BK−/− ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK−/− permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK−/− hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK−/− hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK−/− hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations. 相似文献
84.
Roel GW Verhaak Frank JT Staal Peter JM Valk Bob Lowenberg Marcel JT Reinders Dick de Ridder 《BMC bioinformatics》2006,7(1):105-15
Background
Intensity values measured by Affymetrix microarrays have to be both normalized, to be able to compare different microarrays by removing non-biological variation, and summarized, generating the final probe set expression values. Various pre-processing techniques, such as dChip, GCRMA, RMA and MAS have been developed for this purpose. This study assesses the effect of applying different pre-processing methods on the results of analyses of large Affymetrix datasets. By focusing on practical applications of microarray-based research, this study provides insight into the relevance of pre-processing procedures to biology-oriented researchers. 相似文献85.
Experimental measurement of particle size distribution and voidage in an expanded bed adsorption system 总被引:2,自引:0,他引:2
This paper presents an experimental analysis of matrix bead size distribution and voidage variations with axial height in an expanded bed adsorption system. Use of a specially constructed expanded bed with side ports has enabled sampling from within the expanded bed along the vertical axis. Particles removed from within the bed were measured for their size distributions. Residence time distribution studies were used to estimate bed voidage. Measurements of axial and radial particle size distributions and axial voidage distribution have been made at different flow rates. Particle size was found to be radially constant, indicating constant stratification in the column. The particle size was found to decrease with increasing axial height. Voidage increased with axial height from a settled bed value of 0.39 to approaching unity for high liquid velocities and increased at a constant axial position with increased flowrate. This information provides key insight into bed stability and data for the improved modeling of this important unit operation. 相似文献
86.
We study the mathematical solutions to the kinetic equations arising from various simple ligand-receptor [corrected] models. Focusing on the prediction of the various models for the activity vs. concentration curve, we find that solutions to the kinetic equations arising from the so-called dimer model exhibit features observed in some experiments, most noticeably a distinct maximum in the activity curve. 相似文献
87.
Identification and characterisation of a novel splice variant of the human CB1 receptor 总被引:4,自引:0,他引:4
Ryberg E Vu HK Larsson N Groblewski T Hjorth S Elebring T Sjögren S Greasley PJ 《FEBS letters》2005,579(1):259-264
Cannabinoid ligands are implicated in many physiological processes and to date two receptors have been identified. However, a growing body of evidence exists that suggests the presence of additional receptors. Whilst cloning the previously described hCB1a, we have identified a novel variant that we call hCB1b. Characterising these two splice variants demonstrates that they have a unique pharmacological profile and that their RNA's are expressed at low levels in a variety of tissues. 相似文献
88.
DNA-protein cross-links are generated by both endogenous and exogenous DNA damaging agents, as intermediates during normal DNA metabolism, and during abortive base excision repair. Cross-links are relatively common lesions that are lethal when they block progression of DNA polymerases. DNA-protein cross-links may be broadly categorized into four groups by the DNA and protein chemistries near the cross-link and by the source of the cross-link: DNA-protein cross-links may be found (1) in nicked DNA at the 3' end of one strand (topo I), (2) in nicked DNA at the 5' end of one strand (pol beta), (3) at the 5' ends of both strands adjacent to nicks in close proximity (topo II; Spo 11), and (4) in one strand of duplex DNA (UV irradiation; bifunctional carcinogens and chemotherapeutic agents). Repair mechanisms are reasonably well-defined for groups 1 and 3, and suggested for groups 2 and 4. Our work is focused on the recognition and removal of DNA-protein cross-links in duplex DNA (group 4). 相似文献
89.
The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity
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Helene Speyer Hans Christian Brix Nørgaard Merete Birk Mette Karlsen Ane Storch Jakobsen Kamilla Pedersen Carsten Hjorthøj Charlotta Pisinger Christian Gluud Ole Mors Jesper Krogh Merete Nordentoft 《World psychiatry》2016,15(2):155-165
Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel‐group, superiority, multi‐centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10‐year risk of cardiovascular disease assessed post‐treatment and standardized to age 60. At follow‐up, the mean 10‐year risk of cardiovascular disease was 8.4 ± 6.7% in the group receiving lifestyle coaching, 8.5 ± 7.5% in the care coordination group, and 8.0 ± 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity. 相似文献
90.
Effects of nucleotide sequence alignment on phylogeny estimation: a case study of 18S rDNAs of apicomplexa 总被引:13,自引:5,他引:8
The reconstruction of phylogenetic history is predicated on being able to
accurately establish hypotheses of character homology, which involves
sequence alignment for studies based on molecular sequence data. In an
empirical study investigating nucleotide sequence alignment, we inferred
phylogenetic trees for 43 species of the Apicomplexa and 3 of Dinozoa based
on complete small-subunit rDNA sequences, using six different
multiple-alignment procedures: manual alignment based on the secondary
structure of the 18S rRNA molecule, and automated similarity-based
alignment algorithms using the PileUp, ClustalW, TreeAlign, MALIGN, and SAM
computer programs. Trees were constructed using neighboring-joining,
weighted-parsimony, and maximum- likelihood methods. All of the multiple
sequence alignment procedures yielded the same basic structure for the
estimate of the phylogenetic relationship among the taxa, which presumably
represents the underlying phylogenetic signal. However, the placement of
many of the taxa was sensitive to the alignment procedure used; and the
different alignments produced trees that were on average more dissimilar
from each other than did the different tree-building methods used. The
multiple alignments from the different procedures varied greatly in length,
but aligned sequence length was not a good predictor of the similarity of
the resulting phylogenetic trees. We also systematically varied the gap
weights (the relative cost of inserting a new gap into a sequence or
extending an already-existing gap) for the ClustalW program, and this
produced alignments that were at least as different from each other as
those produced by the different alignment algorithms. Furthermore, there
was no combination of gap weights that produced the same tree as that from
the structure alignment, in spite of the fact that many of the alignments
were similar in length to the structure alignment. We also investigated the
phylogenetic information content of the helical and nonhelical regions of
the rDNA, and conclude that the helical regions are the most informative.
We therefore conclude that many of the literature disagreements concerning
the phylogeny of the Apicomplexa are probably based on differences in
sequence alignment strategies rather than differences in data or
tree-building methods.
相似文献