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At least 469 records · Page 26Linked to original sources
PubMed2004

Apoptosis and systemic lupus erythematosus.

Reduced clearance of dying cells by macrophages or increased apoptosis provokes accumulation of cellular fragments in various tissues. This process seems to induce the uptake of autoantigens from apoptotic nuclei or chromatin by dendritic cells (DCs). Then, the DCs present altered self-epitopes to naive T cells. Thus, autoreactive T cells are activated accidentally and may now provide T-cell help for B cells that present peptides processed from secondary necrotic/late apoptotic prey. Impaired phagocytic removal of early apoptotic cells may cause accumulation of secondary necrotic cells and debris in the germinal centers of secondary lymph organs. The latter bind complement and can, therefore, be trapped on the surfaces of follicular DCs (FDCs). B cells may get in contact with intracellular autoantigens that had been released during late stages of apoptotic cell death and are immobilized by FDCs. Consecutively, B cells that had, for example, gained specificity for nuclear auto-antigens during random somatic mutations can receive a short-term survival signal. After migration into the mantle zone, these autoreactive B cells may finally be activated by autoreactive CD4+ T helper cells. B cells then differentiate into memory or plasma cells. The plasma cells produce those pathogenic nuclear autoantibodies. Many defects are known with respect to the clearance of apoptotic cells and cell material, especially that of nuclear origin. Reflecting on the plethora of defects of clearance of apoptotic material already demonstrated in systemic lupus erythematosus, it is reasonable to argue that, for many patients, failure of clearance is at the heart of their disease.

Apoptosis↗
PubMed2002

Toward a theory of intracrine hormone action.

A growing body of evidence indicates that in some cases, peptide hormones can function in the intracellular space. These findings are reviewed. In addition, this laboratory has made proposals regarding the origin, nature and function of intracrines--that is, intracellularly acting peptide hormones that also function in an autocrine, paracrine or endocrine manner. Here, these hypotheses are developed, and potential implications/applications of this point of view are discussed. Possible implications for cellular differentiation, cellular memory and hormonal responsiveness, as well as for the assumption of novel functions by intracellular regulatory proteins are discussed.

Angiotensins↗
PubMed1999

Analysis of the cord blood T lymphocyte response to superantigen.

We have characterized the T lymphocyte population of the human neonate in respect of the expression of phenotypic profiles for naive, memory and differentiated populations. We have examined the response of the neonate T cell to the superantigen Staphylococcus enterotoxin B (SEB) and compared the response to T cells from healthy adults. We found that the primary response to SEB is equivalent in neonates and adults but that the secondary response demonstrates hyporesponsiveness in the neonate that is more profound than in adults. This response was associated with increased expression of CD25; the alpha chain of the IL-2 receptor, equivalent to that seen in responding cells from adults. A modest increased expression of CD122 and CD132, the beta and gamma chains of the IL-2 receptor, was also observed. There was no increase in the IL-4 receptor (CD124). The hyporesponsive neonate T cells proliferated in response to exogenous IL-2 but the response was less than none SEB treated cells. The neonate cells did not respond to IL-4. We also examined the expression of MHC class II molecules on SEB stimulated cells and found that both neonate and adult T cells upregulate MHC class II to a similar degree. The difference in the hyporesponsive cells appears to result in part from a lower production of IL-2 and in part from a lower ability of cord cells to respond to IL-2. Since the stimulated cord cells expressed IL-2 receptor at the same levels as similarly treated adult cells; there may be differences in down stream signaling pathways.

Adult↗
PubMed1999

Airway nerves and protein phosphatases.

Much attention has focused on the important role played by phosphatases in the control of gene transcription, cell differentiation and memory regulation. It is also clear that phosphatases may regulate a number of biochemical pathways which can modulate cellular function. Of particular interest is the role of phosphatases in the control of neuronal function. Alterations in neuronal function may contributed to the heightened airways responsiveness observed in asthma to a number of physiological stimuli including distilled water, sulfur dioxide, metabisulfite, hypertonic saline, exercise, allergens, viruses and cold air. An understanding of the mechanisms which regulate the function of sensory nerves could have important clinical implications. In this review we will highlight a number of studies that have investigated the role of phosphatases in the regulation of airway nerve function.

Bronchi↗
PubMed2002

Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory.

Nicotine and other nicotinic receptor agonists have been found in a variety of studies to improve memory, while nicotinic receptor blockade can impair memory. The critical neural mechanisms for nicotinic involvement with memory are still under investigation. Initial evidence supports the involvement of the ventral hippocampus. Lesions in this area block nicotine-induced memory improvement and mecamylamine-induced impairment. Local ventral hippocampal application of the nicotinic channel blocker mecamylamine impairs memory in the 8-arm radial maze. Both alpha 4 beta 2 and alpha 7 nicotinic receptors seem to be involved. Ventral hippocampal infusions of high doses of the alpha 4 beta 2 nicotinic antagonist dihydro-beta-erythrodine (DH beta E) and the alpha 7 nicotinic antagonist methyllycaconitine (MLA) impair memory performance on the 8-arm radial maze. However, high doses of these drugs may limit specificity and they cause preconvulsant effects, which in themselves may affect memory. The current study used the more challenging 16-arm radial maze to determine the effects of lower doses of these drugs on memory and to differentiate effects on working and reference memory. Adult female Sprague-Dawley rats were trained on a working and reference memory task in the 16-arm radial maze and then were implanted with bilateral chronic guide cannulae directed to the ventral hippocampus. After recovery from surgery, the rats received acute intrahippocampal infusions of dose combinations of DH beta E and MLA. In the first study, DH beta E (0 and 6.75 microg/side) and MLA (0, 6.75, 13.5 and 27 microg/side) were administered in a counter-balanced order. In the second study, lower doses of DH beta E (0, 1.6375, 3.275 and 6.75 microg/side) were administered alone or with MLA (0 and 6.75 microg/side) in a counter-balanced order. In the first study, DH beta E caused a significant increase in both working and reference memory errors. MLA at a dose of 27 microg/side caused a significant increase in working memory errors, but this dose had no significant effect on reference memory errors. Interestingly, no additive effects were seen with combined administration of DH beta E and MLA in this study, and at the doses used, no effects were seen on response latency. In the second study, lower doses of DH beta E did not cause a significant deficit in working memory performance. Co-administration of MLA with these subthreshold doses did precipitate a memory impairment. The current results confirm the specificity of the memory deficits caused by these drugs. These results support the involvement of alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus as being critical for memory function.

Acetylcholine↗
PubMed2000

The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis.

T lymphocyte activation evokes distinct changes in cell surface O-glycans. CD8+ T cells undergo an elimination of sialic acid on core 1 O-glycans and an induction of core 2 O-glycans until either apoptotic death or differentiation into memory cells. We find that the ST3Gal-I sialyltransferase is required for core 1 O-glycan sialylation and its deficiency induces core 2 O-glycan biosynthesis. Apoptosis ensues with the loss of peripheral CD8+ T cells in the absence of immune stimulation. Cell surface ligation of the ST3Gal-I substrate CD43 recapitulates this phenotype by a caspase 3-independent mechanism. Control of core 1 O-glycan sialylation in T lymphocytes by ST3Gal-I comprises a homeostatic mechanism that eliminates CD8+ T cells by apoptosis while facilitating the production of viable CD8+ memory T cells.

Animals↗
PubMed1998

Humoral immunity due to long-lived plasma cells.

Conventional models suggest that long-term antibody responses are maintained by the continuous differentiation of memory B cells into antibody-secreting plasma cells. This is based on the notion that plasma cells are short-lived and need to be continually replenished by memory B cells. We examined the issue of plasma cell longevity by following the persistence of LCMV-specific antibody and plasma cell numbers after in vivo depletion of memory B cells and by adoptive transfer of virus-specific plasma cells into naive mice. The results show that a substantial fraction of plasma cells can survive and continue to secrete antibody for extended periods of time (>1 year) in the absence of any detectable memory B cells. This study documents the existence of long-lived plasma cells and demonstrates a new mechanism by which humoral immunity is maintained.

Adoptive Transfer↗
PubMed2003

Emergence of complex behaviour from simple circuit structures.

The set of (feedback) circuits of a complex system is the machinery that allows the system to be aware of the levels of its crucial constituents. Circuits can be identified without ambiguity from the elements of the Jacobian matrix of the system. There are two types of circuits: positive if they comprise an even number of negative interactions, negative if this number is odd. The two types of circuits play deeply different roles: negative circuits are required for homeostasis, with or without oscillations, positive circuits are required for multistationarity, and hence, in biology, for differentiation and memory. In non-linear systems, a circuit can positive or negative (an 'ambiguous circuit', depending on the location in phase space. Full circuits are those circuits (or unions of disjoint circuits) that imply all the variables of the system. There is a tight relation between circuits and steady states. Each full circuit, if isolated, generates steady state(s) whose nature (eigenvalues) is determined by the structure of the circuit. Multistationarity requires the presence of at least two full circuits of opposite Eisenfeld signs, or else, an ambiguous circuit. We show how a significant part of the dynamical behaviour of a system can be predicted by a mere examination of its Jacobian matrix. We also show how extremely complex dynamics can be generated by such simple logical structures as a single (full and ambiguous) circuit.

Feedback↗
PubMed2004

Sensitization of T cells to apoptosis--a role for ROS?

T cell homeostasis is achieved by balancing the production and proliferation of T cells with their apoptotic cell death. Activation of naïve T cells by antigen in the context of MHC results in the massive expansion of antigen-specific T cells and the production of reactive oxygen species (ROS). Following expansion, the majority of the T cells die via apoptosis, while a small number of them survive and differentiate into memory T cells. This cell fate decision is crucial to our understanding of how autoimmunity is avoided and how immunity is maintained. It has become increasingly clear that ROS can affect this cell fate decision by sensitizing T cells to apoptosis. Interestingly, ROS have effects on both intrinsic and extrinsic apoptosis pathways through modulation of expression of the major molecules in these pathways, Bcl-2 and FasL. In this review, we will focus on the pro-apoptotic effects of ROS and mechanisms by which they regulate the death of T cells.

Animals↗
PubMed1996

Memory for and experience of differential competitive behavior of individuals and groups.

Four experiments investigated whether differential experiences with groups and individuals led to previously obtained results of greater competitive expectations in intergroup than interindividual relations. In Experiment 1, participants rated their recalled instances of intergroup relations as more competitive than their interindividual relations. In Experiment 2, a relatively greater proportion of competitive to cooperative intergroup relations were recalled compared with interindividual relations. In Experiment 3, participants recorded relevant interactions for 7 days, and rated their intergroup relations as more competitive than their interindividual relations. In Experiment 4, participants recorded a relatively greater number of cooperative than competitive relations with individuals than with groups. These results can be interpreted as a demonstration in a nonlaboratory context that intergroup relations are more competitive than interindividual relations.

Adolescent↗
PubMed1989

Bizarre imagery, interference, and distinctiveness.

Previous studies have shown that bizarre and common images produce equivalent levels of recall in unmixed-list designs. Using unmixed lists, we tested the view that bizarre images would be less susceptible than common images to common sources of interference. In all experiments, subjects imaged a list of either bizarre or common sentences and then performed some kind of interfering task before recalling the initial list of sentences. Experiment 1 showed that bizarre images were better accessed than common images after imaging an intervening list of common sentences. Also, components of common images tended to be better recalled than those of bizarre images after imaging an intervening list of bizarre sentences. Experiments 2a and 2b showed that interfering tasks consisting of studying lists of common concrete nouns did not differentially affect memory for bizarre and common images. In Experiment 3, labeling and imaging an interfering list of common pictures produced higher recall of bizarre images. Generally, bizarre images appeared to be less susceptible than common images to interference from certain types of common encodings. Importantly, the superior recall of bizarre images was always due to greater image (sentence) access, whereas higher recall of common images was associated with greater recovery of the image (sentence) constituents. Explanation of the precise pattern of results requires consideration of the distinctive properties of bizarre images.

Attention↗
PubMed1995

Differential effects of aging on memory for content and context: a meta-analysis.

The authors reviewed the evidence of age differences in episodic memory for content of a message and the context associated with it. Specifically, the authors tested a hypothesis that memory for context is more vulnerable to aging than memory for content. In addition, the authors inquired whether effort at encoding and retrieval and type of stimulus material moderate the magnitude of age differences in both memory domains. The results of the meta-analysis of 46 studies confirmed the main hypothesis: Age differences in context memory are reliably greater than those in memory for content. Tasks that required greater effort during retrieval yielded larger age differences in content but not in context memory. The greatest magnitude of age differences in context memory was observed for those contextual features that were more likely to have been encoded independently from content. Possible mechanisms that may underlie age differences in context memory-attentional deficit, reduced working memory capacity, and failure of inhibitory processing are discussed.

Adult↗
PubMed1993

Memory for self-generated narration in the elderly.

The story mnemonic technique, an effective encoding and retrieval strategy for young adults, was used as a procedure to study encoding and recall in elderly women. Experiment 1 (15 undergraduate and 14 elderly women) showed the technique to be reliable over 3 weeks and without practice effects in both age groups. In Experiment 2, 67 elderly women (mean age = 72 years) were found to make up 3 distinctive subgroupings in patterns of narration cohesiveness and recall accuracy, consistent with pilot data on the technique. A stepwise multiple regression equation found narration cohesiveness, an adaptation of the Daneman-Carpenter (1980) working-memory measure and vocabulary to predict word recall. Results suggested that a general memory factor differentiated the 3 elderly subgroups.

Adolescent↗
PubMed2006

The differential effects of stress on memory consolidation and retrieval: a potential involvement of reconsolidation? Theoretical comment on Beckner et al. (2006).

Previous experiments in the field of stress and memory have suggested a facilitative effect of stress hormones on the consolidation of information but an impairing effect on the retrieval of information. In the article "Stress Facilitates Consolidation of Verbal Memory for a Film but Does Not Affect Retrieval," V. E. Beckner, D. M. Tucker, Y. Delville, and D. C. Mohr (2006) report that exposure to an anticipatory psychological stress enhances consolidation, although it has no impact on the retrieval of previously learned information. This finding is discussed around the importance of the environmental context in which stress is applied and memory is measured. Here, the authors raise the possibility that the enhancing effects of stress on consolidation as reported by Beckner et al. may be explained by the fact that stress can act as a reactivation cue, leading to a 2nd round of consolidation, a process called reconsolidation.

Hormones↗
PubMed2005

Recognition of lipid antigens by T cells.

Recent studies have shown that the recognition of lipid antigens by the immune system is important for defence against infection and other diseases, and that lipid-specific responses occur at higher frequencies than previously suspected. Thanks to several recent advances in this field, we now have a better appreciation of the molecular and cellular requirements of T-cell stimulation by lipids. These findings have raised new questions about the mechanisms of lipid presentation, the priming and clonal expansion of lipid-specific T cells, and their differentiation into memory cells. A greater understanding of lipid-specific T cells and the molecular mechanisms of lipid immunogenicity should facilitate the development of lipid-based vaccines.

Animals↗
PubMed2004

Acute stress enhances memory for emotional words, but impairs memory for neutral words.

This article examined effects of acute stress on memory for neutral and emotional words. Participants (n = 40) were exposed to either a psychosocial stressor or a control task, followed by a memory test. The stress hormone cortisol was measured in saliva before and after stress induction and after the memory test. Acute stress had a differential effect on memory such that recall of neutral words was impaired, whereas that of emotional words was enhanced. These effects on memory performance were not mediated by cortisol. The authors conclude that it makes little sense to speculate about memory effects and elevated levels of cortisol because such effects might depend on the valence of the material that is learned.

Adult↗
PubMed1986

Paired associate learning: normative data for differences between high and low associate word pairs.

Wilson, Bacon, Kaszniak, and Fox (1982) suggest that the learning of low associate pairs on the Wechsler Memory Scale involves episodic memory alone while the learning of high associate pairs involves semantic memory as well. Tulving (1983) also comments that, whereas some information in episodic memory is relatively unorganized and access to its content tends to be deliberate and requiring conscious effort (e.g., low associate pairs), information in semantic memory is organized and access to its content is more automatic (e.g., high associate pairs). As there may be occasions when it would be useful to compare these two types of memory functioning, differential diagnosis between depressive pseudodementia and organic dementia for example, normative data is provided enabling the calculation of the frequency with which differences between the learning of the two kinds of associate occur, based on the performance of 500 subjects with no known neuropsychiatric involvement.

Adult↗