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141.
Activation-induced polarized recycling targets T cell antigen receptors to the immunological synapse; involvement of SNARE complexes 总被引:5,自引:0,他引:5
Das V Nal B Dujeancourt A Thoulouze MI Galli T Roux P Dautry-Varsat A Alcover A 《Immunity》2004,20(5):577-588
The mechanism by which T cell antigen receptors (TCR) accumulate at the immunological synapse has not been fully elucidated. Since TCRs are continuously internalized and recycled back to the cell surface, we investigated the role of polarized recycling in TCR targeting to the immunological synapse. We show here that the recycling endosomal compartment of T cells encountering activatory antigen-presenting cells (APCs) polarizes towards the T cell-APC contact site. Moreover, TCRs in transit through recycling endosomes are targeted to the immunological synapse. Inhibition of T cell polarity, constitutive TCR endocytosis, or recycling reduces TCR accumulation at the immunological synapse. Conversely, increasing the amount of TCRs in recycling endosomes before synapse formation enhanced their accumulation. Finally, we show that exocytic t-SNAREs from T cells cluster at the APC contact site and that tetanus toxin inhibits TCR accumulation at the immunological synapse, indicating that vesicle fusion mediated by SNARE complexes is involved in TCR targeting to the immunological synapse. 相似文献
142.
Delaugerre C Teglas JP Treluyer JM Vaz P Jullien V Veber F Rouzioux C Chaix ML Blanche S 《Journal of acquired immune deficiency syndromes (1999)》2004,37(2):1269-1275
Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level. 相似文献
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Kannangai R Ramalingam S Vijayakumar TS Vincent AA Abraham OC Subramanian S Rupali P Mathai D Jesudason MV Sridharan G 《Indian journal of medical microbiology》2003,21(4):274-276
Currently, antiretroviral therapy has become more affordable even in developing countries and it is being used in India. Fifteen HIV-1 infected individuals, who were on highly active antiretroviral therapy (HAART), were followed up for an average period of one year. The plasma viral load and CD4+ T cell estimation done at mean intervals of 5 months and 11 months after initiation of therapy showed a good response to therapy in 14 (93%) individuals. 相似文献
146.
Listeria--review of epidemiology and pathogenesis. 总被引:2,自引:0,他引:2
Vidhya Ramaswamy Vincent Mary Cresence Jayan S Rejitha Mohandas Usha Lekshmi K S Dharsana Suryaprasad Priya Prasad Helan Mary Vijila 《Journal of microbiology, immunology, and infection》2007,40(1):4-13
Listeria monocytogenes (commonly called Listeria) is a Gram-positive facultatively intracellular foodborne pathogen often found in food and elsewhere in nature. It can cause a rare but serious disease called listeriosis, especially among pregnant women, the elderly or individuals with a weakened immune system. In serious cases, it can lead to brain infection and even death. Listeria is more likely to cause death than other bacteria that cause food poisoning. In fact, 20 to 30% of food borne listeriosis infections in high-risk individuals may be fatal. Recent technological developments have increased the ability of scientists to identify the cause of foodborne illnesses. L. monocytogenes has been used as a model organism for the study of intracellular parasitism. Whilst the basic mechanisms of cellular pathogenesis have been elucidated by a series of elegant studies, recent research has begun to focus upon the gastrointestinal phase of L. monocytogenes infection. Epidemiological studies of outbreaks of human disease now demonstrate that the pathogen can cause gastroenteritis in the absence of invasive disease and associated mortality. Elucidation of whole genome sequences and virulence determinants have greatly contributed to understanding of the organism and its infection pathways. 相似文献
147.
Brites P Motley AM Gressens P Mooyer PA Ploegaert I Everts V Evrard P Carmeliet P Dewerchin M Schoonjans L Duran M Waterham HR Wanders RJ Baes M 《Human molecular genetics》2003,12(18):2255-2267
Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder. 相似文献
148.
Marcie R Finney Nicholas J Greco Stephen E Haynesworth Joseph M Martin David P Hedrick Jimmy Z Swan Daniel G Winter Suzanne Kadereit Matthew E Joseph Pingfu Fu Vincent J Pompili Mary J Laughlin 《Biology of blood and marrow transplantation》2006,12(5):585-593
Endothelial precursor cells (EPCs) cultured from adult bone marrow (BM) have been shown to mediate neovasculogenesis in murine models of vascular injury. We sought to directly compare umbilical cord blood (UCB)- and BM-derived EPC surface phenotypes and in vivo functional capacity. UCB and BM EPCs derived from mononuclear cells (MNC) were phenotyped by surface staining for expression of stromal (Stro-1, CXCR4, CD105, and CD73), endothelial (CD31, CD146, and vascular endothelial [VE]-cadherin), stem cell (CD34 and CD133), and monocyte (CD14) surface markers and analyzed by flow cytometry. The nonobese diabetic/severe combined immunodeficiency murine model of hind-limb ischemia was used to analyze the potential of MNCs and culture-derived EPCs from UCB and BM to mediate neovasculogenesis. Histologic evaluation of the in vivo studies included capillary density as a measure of neovascularization. Surface CXCR4 expression was notably higher on UCB-derived EPCs (64.29%+/-7.41%) compared with BM (19.69%+/-5.49%; P=.021). Although the 2 sources of EPCs were comparable in expression of endothelial and monocyte markers, BM-derived EPCs contained higher proportions of cells expressing stromal cell markers (CD105 and CD73). Injection of UCB- or BM-derived EPCs resulted in significantly improved perfusion as measured by laser Doppler imaging at days 7 and 14 after femoral artery ligation in nonobese diabetic/severe combined immunodeficiency mice compared with controls (P<.05). Injection of uncultured MNCs from BM or UCB showed no significant difference from control mice (P=.119; P=.177). Tissue samples harvested from the lower calf muscle at day 28 demonstrated increased capillary densities in mice receiving BM- or UCB-derived EPCs. In conclusion, we found that UCB and BM-derived EPCs differ in CXCR4 expression and stromal surface markers but mediate equivalent neovasculogenesis in vivo as measured by Doppler flow and histologic analyses. 相似文献
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