Serum‐free culture conditions to generate immature human monocyte‐derived DC (Mo‐DC) were optimized, and the parameters that influence their maturation after exposure to lipopeptides containing CD4+ ...and CD8+ T‐cell epitopes were examined. The lipopeptides contained a single CD4+ helper T‐cell epitopes, one of a number of human leucocyte antigen (HLA)‐A2‐restricted cytotoxic T‐cell epitope and the lipid Pam2Cys. To ensure complete maturation of the Mo‐DC, we examined (i) the optimal lipopeptide concentration, (ii) the optimal Mo‐DC density and (iii) the appropriate period of exposure of the Mo‐DC to the lipopeptides. The results showed that a high dose of lipopeptide (30 μm) was no more efficient at upregulating maturation markers on Mo‐DC than a low dose (6 μm). There was an inverse relationship between Mo‐DC concentration and the mean fluorescence intensity of maturation markers. In addition, at the higher cell concentrations, the chemotactic capacity of the Mo‐DC towards a cognate ligand, CCL21, was reduced. Thus, high cell concentrations during lipopeptide exposure were detrimental to Mo‐DC maturation and function. The duration of exposure of Mo‐DC to the lipopeptides had little effect on phenotype, although Mo‐DC exposed to lipopeptides for 48 rather than 4 h showed an increased ability to stimulate autologous peripheral blood mononuclear cells to release interferon‐γ in the absence of exogenous maturation factors. These findings reveal conditions for generating mature antigen‐loaded DC suitable for targeted immunotherapy.
Grade 91 steel has been used in nuclear and fossil power plants since the 1970s. Manufacturing variabilities resulting from manufacturing, repair, and management activities have been attributed to ...lowered creep and fatigue life. This paper characterizes the elastic, thermal, and anelastic properties of P91 steel with different microstructures. Eight different microstructural conditions were identified as acceptable, gross, and gradual degradations. Ultrasonic testing was used to measure velocities, and resonant ultrasound spectroscopy was used to measure internal friction. The thermal diffusivity was measured along with Vicker's hardness and grain size. A model for internal friction was used to combine the measured elastic and thermal properties. The results suggest that the current understanding of internal friction and its sources may be incomplete for complex microstructures like grade 91. From an nondestructive evaluation perspective, the results suggest that the internal friction has the highest sensitivity to microstructure changes, compared to elastic and thermal properties.
Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for ...non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P = .85), but there were more men in the HCV group (man-woman ratio, 2.1:1v 0.9:1; P = .006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes (P > .05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P = .02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD. (Liver Transpl 2000;6:570-574.)
Objective: To examine racial differences in the secular trends in respiratory-related neonatal mortality among very low birth weight (VLBW) infants in the United States, temporally associated with ...surfactant availability.
Design: Comparison of time trends in African American and non-Hispanic white (NHW) VLBW infants of cause-specific neonatal mortality and neonatal and infant mortality for 2 consecutive 3-year periods.
Results: From 1985 to 1988 there was no racial difference in the rate of decline of each mortality outcome. From 1988 to 1991 rates of decline in neonatal mortality caused by respiratory distress syndrome and by all respiratory causes were significantly greater for NHWs compared with African-Americans. However, the rate of decline in nonrespiratory neonatal mortality was similar for African Americans and NHWs. Compared with African American VLBW infants, NHWs had a greater rate of decline in both neonatal (31% vs 20%; P < .01) and infant mortality (32% vs 21%; P < .01) during this period.
Conclusions: Between 1988 and 1991, declines in neonatal mortality risks caused by respiratory distress syndrome and all respiratory causes were greater for NHW infants than for African American VLBW infants. The decline in nonrespiratory mortality risk showed no racial differences. These findings suggest possible racial disparities in timely access or racial differences in the efficacy of respiratory treatments for VLBW infants.
T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount ...immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+ T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+ T cells. Here, we investigate CD4+ T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+ T cells in five HLA-DR1+ subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.
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•Conserved influenza epitopes are recognized in multiple HLA-DR1+ donors•Shared TRAV-gene usage underpins epitope-specific responses in vitro•Structural analysis identifies biochemical features associated with V-gene selection•CDR3 motifs and enrichments are evident in several shared “public” CDR3 sequences
CD4+ T cells orchestrate protection from severe influenza. However, knowledge of epitopes and the molecular patterns associated with recognition across the population is lacking. Greenshields-Watson et al. identify several influenza epitopes from internal proteins and use them to explore the biochemical features that underpin CD4+ T cell responses to influenza.
Abstract Introduction Proposed diagnostic criteria (international working group and National Institute on Aging and Alzheimer's Association) for Alzheimer's disease (AD) include markers of ...amyloidosis (abnormal cerebrospinal fluid CSF amyloid beta Aβ42) and neurodegeneration (hippocampal atrophy, temporo-parietal hypometabolism on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and abnormal CSF tau). We aim to compare the accuracy of these biomarkers, individually and in combination, in predicting AD among mild cognitive impairment (MCI) patients. Methods In 73 MCI patients, followed to ascertain AD progression, markers were measured. Sensitivity and specificity, positive (LR+) and negative (LR−) likelihood ratios, and crude and adjusted hazard ratios were computed. Results Twenty-nine MCI patients progressed and 44 remained stable. Positivity to any marker achieved the lowest LR− (0.0), whereas the combination Aβ42 plus FDG-PET achieved the highest LR+ (6.45). In a survival analysis, positivity to any marker was associated with 100% conversion rate, whereas negativity to all markers was associated with 100% stability. Discussion The best criteria combined amyloidosis and neurodegeneration biomarkers, whereas the individual biomarker with the best performance was FDG-PET.
To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g.
We did a case-control study in which ...cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test.
Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect.
Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.
A mechanistic study is detailed in which coal ash is heated with its shrinkage measured continuously up to a temperature of 1600°C. The temperatures corresponding to the rapid rate of shrinkage ...correspond to the formation of eutectics identified on phase diagrams. Samples were therefore heated to these temperatures, cooled rapidly and examined using a scanning electron microscope (SEM) to identify the associated chemical and physical changes. The progressive changes in the range of chemical composition (from SEM), the extent of undissolved ash particles and porosity were then quantified and related to homogenisation, viscosity and ash fusion mechanisms. Alternate ash fusion temperatures based on different levels of shrinkage have also been suggested to characterise the ash deposition tendency of the coals.
An alternating direction implicit (ADI) scheme is introduced which is capable of solving a general parabolic equation in two space dimensions with mixed derivative and convective terms. In the case ...of constant coefficients the scheme is shown to be unconditionally stable. The study was motivated by the investigation of flow in a dye laser cell (a device used for the amplification of a laser beam), a simple model for which involves laminar flow in a two-dimensional symmetric channel subject to impulsive heating. Numerical results are presented for this problem, and the qualitative behaviour of the temperature distribution within the channel for different Peclet numbers is discussed.
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