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71.
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74.
López JA Bioley G Turtle CJ Pinzón-Charry A Ho CS Vuckovic S Crosbie G Gilleece M Jackson DC Munster D Hart DN 《Journal of immunological methods》2003,274(1-2):47-61
Dendritic cells (DC) for cancer immunotherapy protocols are generated most commonly by in vitro differentiation of monocytes with exogenous cytokines (Mo-DC). However, Mo-DC differ in their molecular phenotype and function from blood DC (BDC). Clinical isolation of BDC has been limited to the use of density gradients, which result in low yields of variable purity. We have developed a DC enrichment platform, which uses the CMRF-44 (IgM) or CMRF-56 (IgG) monoclonal antibodies (mAb) to select BDC that express these antigens after a short overnight incubation. After culture of peripheral blood mononuclear cells (PBMC) in autologous/AB serum, biotinylated CMRF-44 was used to select DC in a single step immuno-magnetic bead procedure; this produced populations containing up to 99% CMRF-44(+) cells, including up to 67% CMRF-44(+) CD14(-) CD19(-) DC, from an initial starting population of approximately 0.5%. We observed consistent differences in the purities obtained from individual donors with a mean of 54% CMRF-44(+) cells (range 19-99%). Similar results were obtained using biotinylated CMRF-56 mAb, an antibody identifying a comparable population in cultured PBMC. We recovered an average of 54% and 66% of the available BDC in separations performed with the CMRF-44 and CMRF-56 mAb, respectively. The reproducibility of the procedure and the ability to perform it in a closed sterile system makes it suitable for clinical use. Larger scale preparations starting from apheresis derived PBMC will produce sufficient BDC for immunotherapy protocols. The purified BDC elicited strong allogeneic mixed leukocyte reactions and HLA classes II- and I-restricted antigen-specific primary immune responses. 相似文献
75.
A further analysis of 1152 hospital autopsies provides data on inaccuracies of specific diagnoses; there are many examples of overdiagnosis and underdiagnosis. All were encountered in a routine hospital autopsy service and their frequency confirms the importance of the hospital autopsy in medical audit. A knowledge of the misdiagnoses which recur frequently could provide guidance in the selection of cases for autopsy. 相似文献
76.
Fein AJ Plotnikoff RC Wild TC Spence JC 《International journal of behavioral medicine》2004,11(3):135-142
The examination of physical environments to explain and promote physical activity is an important yet under-investigated area
of research inquiry. This study explored relationships between the perceived availability of physical environmental resources
and the perceived importance of these resources in relation to physical activity levels amongst youth. A self-report questionnaire
was completed by 610 students (mean age = 15.5 years old; 62% female participants) from four high schools (grades 9-12) in
rural Alberta, Canada. Perceived physical environment constructs explained 5% of the variance in physical activity, with home,
neighborhood, and school as significant domains. Perceived importance constructs explained 8% of the variance in physical
activity with school context showing the only significant relationship with physical activity. A hierarchical regression analysis
entered sex, grade, self-efficacy, peer, family and physical education teacher relationships, as the first block and eight
environmental constructs as the second block. The first block variables accounted for 22% of the variance and environmental
constructs accounted for an added 4% of the variance in physical activity. Perceived importance of the school environment
was the only environment variable significantly associated with physical activity (β = .14; p < .05) after taking into account
the impact of these traditional predictors. These findings reinforce the need to provide and support school physical environments
related to physical activity. 相似文献
77.
We have cloned and characterized the Drosophila X virus (DXV) genome segment B and its encoded VP1, the putative RNA-dependent RNA polymerase (RdRp) present in the virion. The 2991-bp open reading frame encodes the largest birnavirus VP1 at 977 aa, with a calculated M(r) of 112.8 kDa. As with the VP1 proteins of the type species of the other two genera in the family Birnaviridae, namely, infectious pancreatic necrosis virus (genus Aquabirnavirus) and infectious bursal disease virus (genus Avibirnavirus), the DXV (genus Entomobirnavirus) VP1 protein contains a consensus GTP-binding site and appears to possess self-guanylylation activity. All of the birnavirus VP1 proteins contain conserved RdRp motifs that reside in the catalytic "palm" domain of all classes of polymerases. However, the birnavirus RdRps lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain of other RdRps. All three birnavirus RdRps do contain downstream DD motifs that could function as part of the catalytic triad. These motifs are, however, located in spatially distinct regions of the various birnavirus VP1 proteins. These results suggest that the VP1 proteins of birnaviruses form a defined subgroup of polymerases that either are lacking the conserved RdRp motif VI or have repositioned this motif to different structural regions. 相似文献
78.
Swartz MJ Batra SK Varshney GC Hollingsworth MA Yeo CJ Cameron JL Wilentz RE Hruban RH Argani P 《American journal of clinical pathology》2002,117(5):791-796
Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma. 相似文献
79.
CTLA-4 is required for the induction of high dose oral tolerance 总被引:5,自引:3,他引:5
Samoilova EB; Horton JL; Zhang H; Khoury SJ; Weiner HL; Chen Y 《International immunology》1998,10(4):491-498
Mucosal and systemic administrations of high dose antigens induce long-
lasting peripheral T cell tolerance. We and others have shown that high
dose peripheral T cell tolerance is mediated by anergy or deletion and is
preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2
(CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell
activation and immune regulation. In the present study, we examined the
roles of the B7 co-stimulation pathway in the generation of high dose
peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4
interaction at the time of tolerance induction partially prevented T cell
tolerance, whereas selective blockade of B7:CTLA-4 interaction completely
abrogated peripheral T cell tolerance induced by either oral or i.p.
antigens. These results suggest that CTLA-4-mediated feedback regulation
plays a crucial role in the induction of high dose peripheral T cell
tolerance.
相似文献
80.
Bell CJ Wallace JL 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1997,7(4):273-284
Infiltration of leucocytes into the mucosa is a hallmark feature of a number of inflammatory bowel disorders, most notably Crohn's disease and ulcerative colitis. The interactions between circulating leucocytes and the vascular endothelium that permit leucocyte migration to a site of injury or infection are mediated via a variety of adhesion molecules. There is now ample evidence for alterations in adhesion molecule expression and function in inflammatory bowel disorders. This raises the possibility that adhesion molecules could be targets for novel therapies. Indeed, many existing anti-inflammatory drugs are capable of modulating adhesion molecule expression or function. Moreover, intensive research is under way to develop more selective and effective modulators of adhesion molecules, in the hope that they will be useful for treating various inflammatory disorders. 相似文献