| 1. |
- Xu, HT, et al.
(författare)
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Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer
- 2006
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Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 125:4, s. 534-541
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Tidskriftsartikel (refereegranskat)abstract
- We studied the expression of axin and beta-catenin and their relation to clinicopathologic factors in 100 non-small cell lung cancers (NSCLCs) by immunohistochemical analysis. The mutation in exon 3 of the beta-catenin gene was examined by polymerase chain reaction and direct sequencing. Preserved axin expression was significantly higher in well- and moderately differentiated NSCLC samples than in poorly differentiated ones. Reduced membranous expression of beta-catenin was shown in 80 cases, whereas 26 cases had aberrant nuclear expression. Poor differentiation and lymph node metastasis were associated significantly with reduced beta-catenin expression. Lower axin expression was related significantly to higher nuclear beta-catenin expression. However, this study failed to detect any exon 3 mutation in the beta-catenin gene in the 100 NSCLC samples. We conclude that reduced beta-catenin and axin expression might predict poor differentiation in NSCLC. Reduced axin expression, but not mutation in exon 3, might be an important explanation for the abnormal beta-catenin expression in NSCLC.
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| 2. |
- Bjurstöm, Helen, et al.
(författare)
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GABA, a natural immunomodulator of T lymphocytes.
- 2008
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 205:1-2, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM-1 microM), physiological concentrations of GABA present around neurons in the brain. The cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 microM GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory.
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| 3. |
- Liu, Yawei
(författare)
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Neruons; regulators of CNS inflammation
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurons have been neglected as cells with major immune regulatory function. Here, we present novel data demonstrating that neurons are highly immune competent and play crucial role in regulation of T cell response and CNS inflammation. Neurons induce proliferation of activated CD4+T cells via B7-CD28 and TGF-?1-TGF-?R signaling pathways with amplification of TCR signaling and increased phosphorylated ZAP-70, IL-2 and IL-9. Neuron-T cell interaction results in conversion of encephalitogenic T cells to CD25+TGF-?1+CTLA-4+ Tregulatory cells which suppress T cells proliferation and inhibit EAE. The suppression is dependent on CTLA-4 but not TGF-?1. However, autocrine action of TGF-?1 is important for proliferative arrest of Treg cells. Early enrichment of membrane-bound TGF-?1+CD4+ T cells in CNS of EAE mice proceeded by intracellular production of TGF-?1 and generation of CD25+TGF-?1+CTLA-4+ Treg cells, these cells in turn prevent EAE. This reveals the physiological importance of the generation of Treg cells in CNS upon interaction with neurons with a key role to down-regulate CNS inflammation. In addition, neurons upregulate PD-L1 upon interaction with encephalitogenic T cells, which in turns leads to generation of a CD4highPD-L1high T cell population. Mice deficient in IFN-? are defective in upregulation of this pathway. This defect is associated with absence of PD-L1 upregulation on motor neurons in the CNS, defective in situ generation of CD4highPD-L1high T cells as well as augmented EAE. Hence, motor neurons in addition to their capacity to generate Treg cells from committed encephalitogic T cells, are crucial in regulation of CNS inflammation through a secondary mechanism leading to induction of cell cycle arrested of encephalitogenic T cells. CNS is exceptionally sensitive to inflammation-caused damage since post mitotic neurons are incapable of regeneration and loss of neurons is associated with loss of vital functions imperative for survival of organism. Hence, neurons are equipped with delicate regulatory properties to limit inflammation of the CNS.
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| 4. |
- Liu, Yawei, et al.
(författare)
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Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
- 2006
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 12:5, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
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| 5. |
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| 6. |
- Wang, Yawei, et al.
(författare)
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Quantitative structure-activity relationship for prediction of the toxicity of polybrominated diphenyl ether (PBDE) congeners
- 2006
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 64:4, s. 515-524
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Tidskriftsartikel (refereegranskat)abstract
- Levels of Polybrominated diphenyl ether (PBDEs) are increasing in the environment due to their use as flame retardants. The similarities of structure to polychlorinated biphenyl (PCB) congeners suggest that they may share similar toxicological properties, such as hepatic enzyme induction. In this work, quantitative structure-activity relationship (QSAR) models were constructed based on 406 descriptors for the logarithm of toxicology index (aryl hydrocarbon receptor relative binding affinities, AhR, I) of 18 PBDE congeners. The method used for building model is the Heuristic method, which is included in comprehensive descriptors for structural and statistical analysis (CODESSA) software. The best regression model involved four descriptors, which were related to the conformational changes, atomic reactivity, molecular electrostatic field, and non-uniformity of mass distribution in a molecule of PBDEs, etc. The high square of the correlation coefficient R(2)(0.903) showed the model was satisfactory.
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