Long-term T cell memory requires the surface expression of self-peptide/major histocompatibility complex molecules

How memory T cells are maintained in vivo is poorly understood. To address this problem, a male-specific peptide (H-Y) was identified and used to activate female anti-H-Y T cells in vitro. Anti-H-Y T cells survived in vivo for at least 70 days in the absence of antigen. This persistence was not because of the intrinsic ability of memory T cells to survive in vivo. Instead, the survival and function of adoptively transferred memory cells was found to require transporter of antigen protein 1-dependent expression of self-peptide/major histocompatibility complex class I molecules in recipient animals. Therefore, it appears that the level of T cell receptor engagement provided by transporter of antigen protein 1-dependent, self-peptide/major histocompatibility complexes is sufficient to maintain the long-term survival and functional phenotype of memory cells in the absence of persistent antigen. These data suggest that positive selection plays a role not only in T cell development but also in the maintenance of T cell memory.     

Evidence for a cyclic GMP-independent mechanism in the anti-platelet action of S-nitrosoglutathione

Using a directed forgetting task, the authors tested in 2 experiments the hypothesis that repressors would be superior to controls in forgetting negative experimental material. Consistent with previous studies, there was an overall directed forgetting effect, with significantly more to-be-remembered material recalled than to-be-forgotten (TBF) material. In both experiments, repressors forgot more negatively valenced words in the TBF set than did nonrepressors, suggesting that repressors have an enhanced capability for using retrieval inhibition. The data offer preliminary support for a cognitive account of repressors' deficits in recalling negative autobiographical memories.     

Estimation of energy expenditure from heart rate measurements in cattle maintained under different conditions

We examined whether heart rate (HR) could be used to estimate energy expenditure (EE) in cattle. Six Hereford heifers (345 +/- 10.8 kg BW) 12 mo of age were implanted with HR radio transmitters and maintained in individual pens under the following treatments: 1) shade or sun exposure, 2) high- or low-energy diet, and 3) feeding in morning or afternoon. The HR of animals was measured every .5 h during 3 mo; measurements of oxygen consumption and HR were made simultaneously in the morning and in the afternoon while animals were resting and exercising. Average daily HR (52 +/- 4 beats/min) and average daily EE (380 +/- 9 kJ/kg(.75)) in animals on the low-energy diet were less than values in animals on the high-energy diet (94 +/- 4 beats/min and 653 +/- 9 kJ/ kg(.75), respectively). For each animal and within each diet, linear regressions best described the relationship between HR and EE in resting animals, whereas quadratic regressions best described this relationship for exercising animals. The quadratic equation for the exercising animals could also be used for resting animals. In addition, a constant value of EE per heart beat (EE pulse) for each individual resting animal was found and gave accurate estimations. This method was convenient because 1) no exercise equipment was needed to generate the regression equations and 2) EE pulse was less affected by diet than was EE estimated by regression equations. We conclude that HR, a relatively easy measurement, can be useful and accurate in estimating EE. To increase the accuracy of the estimation of EE by HR, the relationship of HR to EE should be established for each animal. In addition, the nutritional regimen for the animal in which EE is estimated should be used for the animal in establishing the relationship.     

The yielding, plastic flow, and fracture behavior of ultra-high molecular weight polyethylene used in total joint replacements

The yielding, plastic flow, and fracture behavior of UHMWPE plays an important role in wear and failure mechanisms of total joint replacement components. The primary objective of this study was to compare the yielding, plastic flow, and fracture behavior of two implantable grades of UHMWPE (GUR 1120 vs 4150 HP). The first part of this work explored the hypothesis that up to the polymer yield point, the monotonic loading behavior of UHMWPE displays similar true stress strain behavior in tension and compression. Uniaxial tension and compression tests were conducted to compare the equivalent true stress vs strain response of UHMWPE up to 0.12 true strain. During monotonic loading, the equivalent true stress strain behavior was similar in tension and compression up to the yield point. However, investigation of the unloading behavior and permanent plastic deformations showed that classical deviatoric rate independent plasticity theory may dramatically overpredict the permanent strains in UHMWPE. A secondary goal of this study was to determine the ultimate true stress and strain for UHMWPE and to characterize the fracture surfaces after failure. Using a fracture mechanics approach, the critical flaw sizes were used in combination with the true ultimate stresses to predict the fracture toughness of the two resins. A custom video-based strain measurement system was developed and validated to characterize the true stress-strain behavior up to failure and to verify the accuracy of the incompressibility assumption in calculating the true stress-strains up to failure. In a detailed uncertainty analysis, theoretical expressions were derived for the relative uncertainty in digital video-based estimates of nominal strain, true strain, homogeneous stress, and true stress. Although the yielding behavior of the two UHMWPE resins was similar, the hardening and plastic flow behavior clearly discriminated between the GUR 1120 and 4150 HP. A statistically significant difference between the fracture toughness of the two resins was also evident. The long-term goal of this research is to provide detailed true stress strain data for UHMWPE under uniaxial tension and compression for future numerical simulations and comparison with more complex multiaxial loading conditions.     

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.     

Smoking and female infertility: a systematic review and meta-analysis

The identification of Ca2+ as a cofactor in photosynthetic O2 evolution has encouraged research into the role of Ca2+ in photosystem II (PSII). Previous methods used to identify the number of binding sites and their affinities were not able to measure Ca2+ binding at thermodynamic equilibrium. We introduce the use of a Ca2(+)-selective electrode to study equilibrium binding of Ca2+ to PSII. The number and affinities of binding sites were determined via Scatchard analysis on a series of PSII membrane preparations progressively depleted of the extrinsic polypeptides and Mn. Untreated PSII membranes bound approximately 4 Ca2+ per PSII with high affinity (K = 1.8 microM) and a larger number of Ca2+ with lower affinity. The high-affinity sites are assigned to divalent cation-binding sites on the light-harvesting complex II that are involved in membrane stacking, and the lower-affinity sites are attributed to nonspecific surface-binding sites. These sites were also observed in all of the extrinsic polypeptide- and Mn-depleted preparations. Depletion of the extrinsic polypeptides and/or Mn exposed additional very high-affinity Ca2(+)-binding sites which were not in equilibrium with free Ca2+ in untreated PSII, owing to the diffusion barrier created by the extrinsic polypeptides. Ca2(+)-depleted PSII membranes lacking the 23 and 17 kDa extrinsic proteins bound an additional 2.5 Ca2+ per PSII with K = 0.15 microM. This number of very high-affinity Ca2(+)-binding sites agrees with the previous work of Cheniae and co-workers [Kalosaka, K., et al. (1990) in Current Research in Photosynthesis (Baltscheffsky, M., Ed.) pp 721-724, Kluwer, Dordrecht, The Netherlands] whose procedure for Ca2+ depletion was used. Further depletion of the 33 kDa extrinsic protein yielded a sample that bound only 0.7 very high-affinity Ca2+ per PSII with K = 0.19 microM. The loss of 2 very high-affinity Ca2(+)-binding sites upon depletion of the 33 kDa extrinsic protein could be due to a structural change of the O2-evolving complex which lost 2-3 of the 4 Mn ions in this sample. Finally, PSII membranes depleted of Mn and the 33, 23, and 17 kDa extrinsic proteins bound approximately 4 very high-affinity Ca2+ per PSII with K = 0.08 microM. These sites are assigned to Ca2+ binding to the vacant Mn sites.