Dendritic Cells as Adjuvants for Immune-mediated Resistance to Tumors

[No abstract available

Clonal expansion of human T lymphocytes initiated by dendritic cells

The accessory cell requirements for cloning T cells in the presence of lectin and T cell growth factors were examined with cells from human peripheral blood. We found that dendritic cells were active and perhaps essential. Single CD4+ lymphocytes could be cloned with 80% efficiency, and CD8+ cells with 50-60% efficiency if 103 syngeneic or allogeneic dendritic cells were added. Some T cell clones developed even with one dendritic cell. Monocytes or B lymphocytes from blood were at least 100-fold weaker in supporting clonal growth. These findings suggest a specialized feeder cell requirement, namely dendritic cells, for cloning T lymphocytes from single resting precursors

Investigating prior parameter distributions in the inverse modelling of water distribution hydraulic models

PublishedJournal Article© 2014 Journal of Mechanical Engineering. All rights reserved. Inverse modelling concentrates on estimating water distribution system (WDS) model parameters that are not directly measurable, e.g. pipe roughness coefficients, which can, therefore, only be estimated by indirect approaches, i.e. inverse modelling. Estimation of the parameter and predictive uncertainty of WDS models is an essential part of the inverse modelling process. Recently, Markov Chain Monte Carlo (MCMC) simulations have gained in popularity in uncertainty analyses due to their effective and efficient exploration of posterior parameter probability density functions (pdf). A Bayesian framework is used to infer prior parameter information via a likelihood function to plausible ranges of posterior parameter pdf. Improved parameter and predictive uncertainty are achieved through the incorporation of prior pdf of parameter values and the use of a generalized likelihood function. We used three prior information sampling schemes to infer the pipe roughness coefficients of WDS models. A hypothetical case study and a real-world WDS case study were used to illustrate the strengths and weaknesses of a particular selection of a prior information pdf. The results obtained show that the level of parameter identifiability (i.e. sensitivity) is an important property for prior pdf selection.We are obliged to Jasper A. Vrugt and Cajo ter Braak for providing the code of the DREAM(ZS) algorithm and graphical post-processing software

Mouse spleen lymphoblasts generated in vitro: Recovery in high yield and purity after floatation in dense bovine plasma albumin solutions*

[No abstract available

Human dendritic cells. Enrichment and characterization from peripheral blood

Previous studies demonstrated that lymphoid tissues of mice and rats contain small numbers (less than 1 percent of nucleated cells) of dendritic cells (DC) with special cytologic, surface, and functional properties. We show here that similar DC represent 0.1-0.5 percent of human peripheral blood mononuclear cells. DC can be enriched to 20-60 percent purity by a multistep procedure analogous to that used in mice. Adherent peripheral blood mononuclear cells are cultured overnight, and the released cells are depleted of monocytes and B cells by readherence to plastic, rosetting with erythrocytes coated with anti-human IgG, and centrifugation in dense albumin columns. Enriched DC have similar cytologic features to rodent DC by light and electron microscopy. DC express HLA, and HLA-DR and the leukocyte-common antigens. They lack phagocytic capacity, receptors for antibody-coated and neuraminidase-treated erythrocytes, surface and intracellular Ig, esterase, peroxidase, and azurophilic granules. DC do not react with several monoclonal antibodies directed to phagocytes (OKM 1, “mac-1,” 63D3, and 61D3) and T cells (OKT 3, 6, 8). Unlike the mouse, human DC express complement receptors. When maintained in culture for 4 d, human DC did not give rise to either B cells or monocytes. Therefore, DC identified by cytologic criteria are distinct from other leukocytes. Enriched populations of DC have been compared to fractions enriched in monocytes, B cells, and T cells in three functional assays: stimulation of the primary allogeneic mixed leukocyte reaction, stimulation of the primary syngeneic MLR, and accessory function for the proliferation of periodate- modified T cells. In each case, the DC fraction was 10-fold or more active than other cell fractions. We conclude that DC circulate in man, and represent the principal cell type required for the initiation of several immune responses

Mouse spleen lymphoblasts generated in vitro: Their replication and differentiation in vitro*

[No abstract available

Non-Newtonian and flow pulsatility effects in simulation models of a stented intracranial aneurysm

Permission to redistribute provided by publishers.Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge'07, are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and wall shear stress (WSS) output are used as a means of comparing the cfd simulations. In addition, a WSS distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. It is concluded that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, to understand dynamic flow effects, and to discriminate more effectively between stent designs. © Authors 2011

Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013.

ObjectiveTo examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia among patients with type 2 diabetes (T2DM).Research design and methodsUsing claims data from 1.66 million privately insured and Medicare Advantage patients with T2DM from 2006 to 2013, we estimated the annual 1) age- and sex-standardized proportion of patients who filled each class of agents; 2) age-, sex-, race-, and region-standardized proportion with hemoglobin A1c (HbA1c) <6%, 6 to <7%, 7 to <8%, 8 to <9%, ≥9%; and 3) age- and sex-standardized rate of severe hypoglycemia among those using medications. Proportions were calculated overall and stratified by age-group (18-44, 45-64, 65-74, and ≥75 years) and number of chronic comorbidities (zero, one, and two or more).ResultsFrom 2006 to 2013, use increased for metformin (from 47.6 to 53.5%), dipeptidyl peptidase 4 inhibitors (0.5 to 14.9%), and insulin (17.1 to 23.0%) but declined for sulfonylureas (38.8 to 30.8%) and thiazolidinediones (28.5 to 5.6%; all P < 0.001). The proportion of patients with HbA1c <7% declined (from 56.4 to 54.2%; P < 0.001) and with HbA1c ≥9% increased (9.9 to 12.2%; P < 0.001). Glycemic control varied by age and was poor among 23.3% of the youngest and 6.3% of the oldest patients in 2013. The overall rate of severe hypoglycemia remained the same (1.3 per 100 person-years; P = 0.72), declined modestly among the oldest patients (from 2.9 to 2.3; P < 0.001), and remained high among those with two or more comorbidities (3.2 to 3.5; P = 0.36).ConclusionsDuring the recent 8-year period, the use of glucose-lowering drugs has changed dramatically among patients with T2DM. Overall glycemic control has not improved and remains poor among nearly a quarter of the youngest patients. The overall rate of severe hypoglycemia remains largely unchanged

Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro

Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span