Migratory properties of naive, effector, and memory CD8(+) T cells.

It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to home to lymphoid organs (central memory cells) or nonlymphoid tissues (effector memory/effector cells). We have shown recently that murine antigen-primed CD8(+) T cells cultured in interleukin (IL)-15 (CD8(IL-15)) resemble central memory cells in phenotype and function. In contrast, primed CD8(+) T cells cultured in IL-2 (CD8(IL-2)) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8(IL-15) cells and, to a lesser degree, CD8(IL-2) cells localized to T cell areas in the spleen, but only naive and CD8(IL-15) cells homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8(IL-15) cells, but not CD8(IL-2) cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8(IL-15) cells to LNs depended on L-selectin and required chemokines that bind CC chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory chemokines and accumulated at sites of inflammation. However, CD8(IL-2) cells were 12 times more efficient in migrating to inflamed peritoneum than CD8(IL-15) cells. Furthermore, CD8(IL-15) cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8(IL-15) cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8(IL-2) effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs.

Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes.

The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T-GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8(+) T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP(+), did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.

A reduced lactate mass explains much of the glycogen sparing associated with training.

Endurance training is associated with glycogen (Gly) sparing, generally attributed to less carbohydrate (CHO) oxidation. However, untrained individuals commit a greater fraction of CHO to lactate (La), accounting for a portion of the Gly "spared." We examined the effects of training (running 1 h/day at 30 m/min up an 8 degrees grade) on whole body CHO distribution and oxidation. Female Long Evans rats (n = 27) were assigned to control (Untr) and trained (Tr) groups. Two days before the experiment, animals were chronically catheterized. On the day of the experiment, animals ran for 20 min at a speed of 28 m/min and were killed with an overdose of pentobarbital sodium injection while running. Whole carcasses were then promptly freeze-clamped with a liquid N2-cooled press. Whole body carcass powder was assayed for La, Gly, and glucose. Resting whole body values were not different between groups (La = 0.78 +/- 0.06 vs. 0.83 +/- 0.07, Gly = 4.46 +/- 0.62 vs. 3.77 +/- 0.35, glucose = 0.19 +/- 0.07 vs. 0.23 +/- 0.09 mmol/body for Tr and Untr rats, respectively). However, postexercise La was higher in Untr vs. Tr group (2.01 +/- 0.28 vs. 1.13 +/- 0.09 mmol/body), and Gly was lower in the Untr vs. Tr rats (1.58 +/- 0.25 vs. 3.42 +/- 0.43 mmol/body). Similarly, Untr animals displayed higher epinephrine levels than Tr at the end of the exercise bout (4.9 +/- 1.0 vs. 1.7 +/- 0.4 ng/ml). Differences between groups in La and glucose masses (postexercise minus rest data) accounted for 60% of the Gly differences. Gly spared from oxidation and replaced by increased fat oxidation only accounted for 40% of the differences in Gly levels between Tr and Untr animals. We conclude that untrained mammals commit a significant portion of their CHO pool to La, which accounts for almost one-half of the apparent Gly spared during moderate-intensity exercise in the trained state.

Hormonal regulation of skeletal muscle hypertrophy in rats: the testosterone to cortisol ratio.

This study determined the influence that the catabolic hormone, corticosterone (C), and the anabolic hormone, testosterone (T), had in regulating skeletal muscle hypertrophy using the rat hind limb ablation model. Specifically, the ratio of T:C (TCR) was manipulated via hormone implants and injections and concentrations measured to evaluate the relative contribution of each hormone to skeletal muscle protein balance. Skeletal muscle growth was measured 16 days after gastrocnemius muscle ablation. Elevations in plasma concentrations of C (via daily C injections, 50 mg kg*kg(-1) body mass) resulted in TCR of 0.007 that was less than the control group TCR of 0.249. In this C-injected group, whole body and skeletal muscle atrophy was elicited-this being greater in the fast-twitch plantaris muscle than in the slow-twitch soleus muscle. The overloaded leg resisted the C-induced atrophy. Castration of animals (TCR 0.024) resulted in less whole body and skeletal muscle growth. However, elevations in plasma concentrations of T (two groups, with TCR of 1.35 and 1.64) did not result in significantly greater muscle growth. Furthermore, T was also ineffective in antagonizing the C-induced atrophy in a group that received both T implants and C injections. This group had a TCR of 0.175 that was similar to the control group ratio of 0.249 that received no manipulations. We concluded that glucocorticoids were able to induce pronounced atrophy, but at the same time overloaded muscles were able to over-ride the glucocorticoid signal. Plasma concentrations of C were a better predictor of muscle growth/atrophy than T and/or the TCR. In addition, it is suggested that the volume of contractile activity of the muscle is perhaps an important determinant of C-induced atrophy, because less atrophy occurs in the more active slow twitch muscles.

The relevance of Noddings' ethics of care to the moral education of nurses.

Noddings' ethics of care is proposed as a model for moral education in nursing. A discussion of Noddings' moral theory is followed by a review of significant criticisms of her theory and her response to these criticisms. Finally, the usefulness of her moral theory as a guide to moral education in nursing is explored.

The use of an advance directive in consultation-liaison psychiatry: a case report.

OBJECTIVE: The following case report illustrates the use of a psychiatric advance directive in a surgical setting. METHOD: The case of a woman with breast cancer and debilitating pre-operative anxiety is presented. Her anxiety was so severe that it resulted in repeated refusal to have necessary surgery. An advance directive facilitated proceeding with surgery despite her objections in the immediate pre-operative period. CONCLUSION: Consultation-Liaison psychiatrists should consider the use of an advance directive when preoperative anxiety interferes with decision-making capacity.

Influence of training on sleeping heart rate following daytime exercise.

The purpose of this investigation was to examine the influence of daytime exercise on heart rate during sleep. Nine, untrained male college students volunteered to participate. They cycled at 75% maximum oxygen uptake, (VO2max) 30 min.day-1 for 12 weeks. The exercise duration was increased by 5 min every 4 weeks from 30 to 40 min per session. Post-training VO2max [mean (SE): 48.9 (1.7) ml.kg-1.min-1] values were significantly (P < 0.01) higher than pre-training [45.5 (1.8) ml.kg-1.min-1] values. Before and after training, sleeping heart rate was assessed on two separate nights. Data were obtained during a night following 30 min of daytime cycling at 75 (6) % VO2max and on a night in which no daytime exercise was performed. A three-way repeated measures ANOVA [training status (pre-/post-training) x activity (exercise day/nonexercise day) x sleep time (18 epochs of 20 min each)] revealed a significant main effect for sleep time (P < 0.001) as well as a sleep time x training status interaction (P < 0.02). No significant difference in sleeping heart rate was noted when exercise and non-exercise days were compared both before and after training. It is concluded that endurance training in these young adult men: (1) hastens the achievement of baseline heart rate during sleep, and (2) does not moderate the relationship between an acute bout of daytime exercise and sleeping heart rate.

The entrepreneurial nurse consultant: a Marxist analysis.

Consultation based on an entrepreneurial model is becoming an increasingly popular career choice for nurses. Marx's theoretical formulations were selected as a framework for examining various aspects of the entrepreneurial model of consultation in nursing. Areas addressed include the growing alienation of nurses from their work in institutional settings, entrepreneurial practice as an escape from alienation, and the inherently conservative nature of entrepreneurial consultant practice.

Feminist pedagogy: nurturing the ethical ideal.

A case study describing a student-teacher interaction is used as a device for examining various models of moral education. The author argues that an ethics of care is foundational to all student-teacher interactions as a means of achieving what Noddings refers to as the primary goal of education: nurturance of the ethical ideal.

Discriminated interresponse times: role of autoshaped responses.

When discriminated interresponse-time (IRT) procedures have been used to assess preference relations among temporally extended operants, deviations from matching have been obtained. Using a yoked-control procedure, the present study found that key pecking in a discriminated IRT procedure has two sources of strength--that arising from the response-reinforcer contingency that is explicitly arranged, and that arising from a stimulus-reinforcer contingency that is a by-product of the explicitly arranged contingency. The key pecking of all lead birds, and that of 3 of the 4 birds exposed to a yoked autoshaping procedure, was controlled by the keylight that signaled the lead birds' criterion IRTs. Because stimulus control of key pecking by the keylight, whether autoshaped or discriminative, fosters deviations from matching, the discriminated IRT procedure does not provide an appropriate basis for conclusions about preference relations among IRTs.

Critique of "The use of animals in nursing research".

The authors present a critique of an article by Cunningham and Mitchell that advocates the use of animals in nursing research. Moral, political, social, and scientific arguments are presented to develop a case in opposition to the use of animals for experimentation. In conclusion, the authors assert that nurse scientists can make a choice at this critical juncture to take another path leading to the maturity of nursing as a research-based profession.

The allocation of time to temporally defined behaviors: responding during stimulus generalization.

In one stimulus condition, reinforcement depended on rats holding a lever for a duration having both minimum and maximum boundaries. During a second light intensity, reinforcement was not available for some rats; for others, reinforcement depended on a second response duration requirement. Generalization test stimuli controlled the same response durations found during training, and the amount of time allocated to a given response duration depended on the proximity of the test stimulus to the training stimulus which controlled that particular duration. The results indicated that a gradient of stimulus control does not reflect an underlying continuous change in responding, but is a result of the mixing of responses previously controlled by stimuli present during conditioning.