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101.
T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis 总被引:2,自引:0,他引:2
Klehmet J Shive C Guardia-Wolff R Petersen I Spack EG Boehm BO Weissert R Forsthuber TG 《Clinical immunology (Orlando, Fla.)》2004,111(1):53-60
Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97-108 (MOG(97-108); TCFFRDHSYQEE), the T cell response diversifies over time to MOG(181-200) (core: MOG(183-191); FVIVPVLGP) and MBP. The spreading epitope MOG(181-200) binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in "humanized" HLA-DR4 transgenic mice. 相似文献
102.
103.
Paola Origone Carlo Bellini Debora Sambarino Barbara Banelli Guido Morcaldi Carmen La Rosa Franco Stanzial Claudio Castellan Domenico A. Coviello Cecilia Garrè Eugenio Bonioli 《Human mutation》2003,22(4):341-341
In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180 相似文献
104.
Franco R Rodríguez R Pasantes-Morales H 《Pflügers Archiv : European journal of physiology》2004,449(2):159-169
Reducing osmolarity by 35% increased 3H-taurine efflux from Swiss 3T3 fibroblasts from 0.5% to a peak of 5.7%. The presence of ATP (10–100 µM; EC50 1.5 µM) increased taurine efflux up to 10%, and decreased the set point for hyposmotically stimulated taurine release (HTR). ATP potentiation was mimicked by UTP, reduced by addition of suramin and pyridoxal phosphate-6-azophenyl-2,4-disulphonic acid (PPADS) and unaffected by ADP, ,-methylene-ATP (,-ATP) or 2-methylthio-ATP (Me-ATP), suggesting its mediation by purinergic P2Y2 and P2Y4 metabotropic receptors. Under isosmotic conditions ATP increased the cytosolic [Ca2+] ([Ca2+]i) markedly, but did not increase taurine release. HTR was independent of external Ca2+ but was reduced (by 56–59%) by BAPTA-AM, thapsigargin-induced depletion of intracellular Ca2+ stores, or phospholipase C (PLC) inhibition. Blockade of calmodulin (CaM) or calmodulin kinase II (CaMKII) reduced HTR by 54% and 76%, respectively. The ATP-mediated potentiation was prevented fully by all these treatments. HTR was reduced by 30–50% by blockers of protein tyrosine kinases (AG18), phosphoinositide 3-kinase (PI3K) (wortmannin), p21rho (toxin B), p21rho-kinase (Y27632) and the stress-activated kinase p38 (PD169316). ATP-mediated potentiation was reduced similarly by these blockers. Simultaneous inhibition of PI3K and CaMKII abolished HTR. Altogether, these results suggest a modulatory effect of ATP, probably exerted by a potentiation of the Ca2+-dependent fraction of HTR. This fraction has as signalling elements a PLC-dependent [Ca2+]i increase, resulting from Ca2+ released from thapsigargin-sensitive internal stores, followed by activation of CaM/CaMKII reactions. The Ca2+/ATP effect operates only when the Ca2+-independent, tyrosine kinase-mediated pathway is already activated. Suggested elements of cross-talk between the two pathways are PLC, PI3K and CaMKII. 相似文献
105.
Franco Laccone Ivonne Jünemann Sharon Whatley Rhian Morgan Rachel Butler Peter Huppke David Ravine 《Human mutation》2004,23(4):395-395
The original article to which this Erratum refers was published in Human Mutation 23:234–244 Human Mutation(2004) 23(3) 234–244 相似文献
106.
Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases. 总被引:2,自引:0,他引:2
Emanuela Maserati Fiorenza Aprili Fabrizio Vinante Franco Locatelli Giovanni Amendola Adriana Zatterale Giuseppe Milone Antonella Minelli Franca Bernardi Francesco Lo Curto Francesco Pasquali 《Genes, chromosomes & cancer》2002,33(1):93-97
The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%. 相似文献
107.
108.
Domenico Lapenna Andrea Mezzetti Sergio de Gioia Agostino Consoli Davide Festi Carmine Di Ilio Franco Cuccurullo 《Pflügers Archiv : European journal of physiology》1994,427(5-6):432-436
The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, -glutamylcysteine synthetase and -glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H2O2-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocarium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury. 相似文献
109.
Resolution and conservation of mismatches in DNA end joining 总被引:1,自引:1,他引:1
Pfeiffer Petra; Thode Silke; Hancke Juliane; Keohavong Phouthone; Thilly William G. 《Mutagenesis》1994,9(6):527-535
DNA end joining is a major pathway for the elimination of double-strandbreaks from chromosomal DNA of higher eucaryotic cells. Extractsof Xenopus laevis eggs rejoin such breaks even when their shortsingle-stranded termini are expected to form imperfectly matchedoverlaps. However, end-joined products cloned in Escherichiacoli, necessarily give rise to perfectly matched products. Thereforeit has not been possible to determine whether the end joiningprocess creates mismatched products, perfectly matched (resolved)products or both. To investigate whether mismatch resolutionwas the result of the X. laevis end joining process or of activitiesof the bacterial host we used denaturing gradient gel electrophoresisto analyse joined products. We found that the end joining processdoes include mismatch resolution, the degree of which varieswith regard to the nature of the original overlap structure.Mismatches 3' to a gap are completely resolved, mismatches 3'to a nick and 5' to a nick or gap are resolved to some extentbut are generally conserved. Mismatches between base matchesare always conserved. These findings suggest competing processesof ligation, DNA fill-in synthesis or exonucleolytic excisionof mismatched bases next to a gap or nick. At mismatches 3'to a nick the probability of ligation is greater than that ofexcision while at mismatches 3' to a gap the probability ofexcision is greater than elongation of a given mismatch. Atmismatches 5' to nicks or gaps it appears that ligation or elongationand ligation, respectively, are the most probable pathways butproducts resulting from mismatch excision, elongation and ligationare also detected.
5To whom correspondence should be addressed 相似文献
110.
Signalling through the death receptor CD95 induces apoptosis by formation of a signalling complex at the cell membrane and subsequent caspase-8 and caspase-3-activation. Treatment of Jurkat T cells with protonophores across the mitochondrial membrane such as 2,4-dinitrophenol (DNP) enhances the death-inducing capacity of CD95. In this study, we show that this enhancement is due to the specific acceleration of caspase-8-processing and activation at the CD95-receptor. DNP-treatment did not affect NF-kappaB-induction by CD95. Immunoprecipitation experiments showed that the amounts of the adapter FADD/MORT1 and pro-caspase-8 at the CD95-receptor were not altered by DNP. Subcellular fractionation studies revealed that the amount of mature caspase-8 but not pro-caspase at the membrane was increased following CD95-stimulation in the presence of DNP. As a consequence of caspase-activation, c-FLIP-levels in the cytosol decreased. In Jurkat cells overexpressing c-FLIPS, DNP was still able to enhance caspase-activation. The enhancing capacity of DNP was seen in some cell lines (Jurkat, CEM and HeLa) but not in SKW6 cells and was also found in mitogen-stimulated human T cells. Furthermore, the enhancement extended to TRAIL-induced caspase-activation. Thus, a mechanism exists by which caspase-8-activation can be accelerated at death receptors and this mechanism can be triggered by targeting mitochondrial oxidative phosphorylation. 相似文献