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Results for “memory differentiation”

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At least 1,063 records · Page 59Linked to original sources
PubMed2001

VIP and PACAP enhance the in vivo generation of memory TH2 cells by inhibiting peripheral deletion of antigen-specific effectors.

In an immune response, antigen-specific CD4 T cells proliferate and differentiate into effector cells capable to produce large amounts of cytokines upon restimulation. Most effector T cells are later eliminated through antigen-induced cell death (AICD), mediated through FasL/Fas interactions. A low percentage of effector T cells survive and differentiate into long-lived memory cells. Mechanisms must operate not only to destroy no longer needed and even potentially damaging T cells, but also to allow the survival of a small number of activated T cells. Little is known about the factors and mechanisms that regulate the shift from an apoptosis-sensitive to an apoptosis-resistant phenotype. VIP and the structurally related peptide, PACAP, synthesized and/or released in the immune organs act on both innate and adaptive immunity. Recently, VIP and PACAP were shown to inhibit AICD in peripheral CD4 T cells by down-regulating FasL expression. In view of these findings, VIP and PACAP are reasonable candidates for the generation of memory T cells. To test this hypothesis, we analyzed the effects of VIP and PACAP in various models for effector and memory T cells. Our data demonstrate that both neuropeptides promote the in vivo effector function and memory phenotype of Th2, but not Th1 cells, by preferentially inhibiting the clonal deletion of Th2 cells. To our knowledge, this is the first report describing the role of a neuropeptide present in the lymphoid microenvironment on the generation and maintenance of long-lived memory T cells.

Adoptive Transfer↗
PubMed1997

Factors controlling the turnover of T memory cells.

Most of the T cells participating in the primary immune response are rapidly eliminated, but small numbers of these cells survive and differentiate into long-lived memory cells. Information on the life history of memory cells can be obtained by studying the component of memory-phenotype T cells found in normal animals; these cells are presumed to represent memory cells specific for various environmental antigens. For CD8+ cells, in vivo exposure to viruses and certain other infectious agents causes a large proportion of memory-phenotype (CD44hi) cells to enter the cell cycle. In this situation, stimulation of CD44hi CD8+ cells does not seem to require T-cell receptor ligation and appears to reflect release of various cytokines, especially type I interferon. The capacity of infectious agents to induce non-antigen-specific stimulation of T cells may play a role in boosting the survival of memory cells and perhaps also in providing an adjuvant function during the primary response.

Animals↗
PubMed2000

[Management of memory disorders in anxious patients consulting a memory clinic].

The proportion of patients consulting pluridisciplinary memory clinics who present anxiety disorders varies with recruitment and referral practices but often exceeded 10p.100. Most of these subjects have an anxiety trait or stress-related generalized anxiety, often triggered by diagnosis of Alzheimer's disease in a close friend or relation. The consultant should play special attention to analyzing the complaint in order to disclose difficulties in attention, true "loss of memory" events, and any recent traumatic events. The psychometric examination is generally normal or evidences discrete frontal dysfunction. Other diagnoses should be ruled out: associated depression, iatrogenic effect, alcoholism, anxiety as a sign of a somatic disease. Management may include drugs, usually on a short term regimen. Short-term psychotherapy or group therapy may be helpful.

Anxiety↗
PubMed1995

Effects of p-chlorophenylalanine-induced depletion of brain serotonin on retrieval of appetitive and aversive memories.

This study examined whether depletion of central serotonin produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given i.c.v. 24 hr later a single dose of p-chlorophenylalanine (p-CPA). (100, 200, 400 micrograms/rat) or drug vehicle. The retention performance and activity were assessed 48 hr after treatment with this depletor. While lower doses of p-CPA selectively reduced serotonin levels in striatum and anterior cortex, higher doses reduced both serotonin and norepinephrine levels in hippocampus in a dose-dependent fashion. The depletor however, failed to produce a differential improvement of aversive memory retrieval. On the contrary, p-CPA reduced the latency to enter both, previously shocked and appetitively reinforced, goalboxes. The enhanced traversing behaviour in T-maze, together with an increased central entry in the open field that observed in depleted groups, might suggest an anxiolytic activity of p-CPA.

Animals↗
PubMed2006

Autocrine and intracrine signaling for cardiogenesis in embryonic stem cells: a clue for the development of novel differentiating agents.

Cardiogenesis, one of the earliest and most complex morphogenetic events in the embryo, is not fully understood at the molecular level and is typically a low-yield process. Affording a high throughput of cardiogenesis from a suitable population of pluripotent cells is therefore a major assignment in the perspective of a stem cell therapy for heart failure. Analysis of cardiac lineage commitment in mouse embryonic stem cells and in vivo models of cardiac differentiation revealed that a number of crucial growth factors are released from precursor cells, acting in an autocrine fashion on specific plasma membrane receptors to prime a cardiogenic decision. Nevertheless, it is increasingly becoming evident that cell nuclei harbor the potential for intrinsic signal transduction pathways. The term "intracrine" has been proposed for growth regulatory peptides that have been shown to act within their cell of synthesis at the level of the nuclear envelope, chromatin, or other subnuclear components. Considerable evidence links known intracrines with transcriptional responses and self-sustaining loops that behave as long-lived signals and impart features characteristic of differentiation, growth regulation and cell memory. This review focuses on a number of autocrine and intracrine systems within the context of cardiac differentiation and emphasizes the identification of cardiogenic mechanisms as a clue for the development of unprecedented differentiating strategies. In this regard, recently synthesized mixed esters of hyaluronan with butyric and retinoic acid primed the expression of cardiogenic genes and elicited a remarkable increase in cardiomyocyte yield in mouse embryonic stem cells. This demonstrates the potential for chemically modifying the gene program of cardiac differentiation without the aid of gene transfer technologies and sets the basis for the design of a novel generation of chemicals suited for the organization of targeted lineage patterning in stem cells.

Animals↗
PubMed1990

Luria Memory Words Test and Wechsler Memory Scale: comparison of utility in discriminating neurologically impaired from controls.

Memory deficits are among the most common initial complaints of patients who are suffering from neurological disorders. The present study compared the relative clinical utility of the Wechsler Memory Scale and the Luria Memory Words Test in differentiating brain-damaged (N = 60) from non-brain-damaged patients (N = 60). Separate stepwise regression analyses selected five variables from each test that accounted for the greatest between-group variance. Separate discriminant functions then were computed that used the WMS and the Luria Words variables selected through the regression analyses. The WMS correctly classified 72% of the subjects, whereas the Luria Words correctly classified 76% of the subjects. A final discriminant function was computed that used all 10 variables and resulted in a classification accuracy of 86%, with 6% false positives and 6% false negatives. Results are discussed relative to the use of each instrument in both a general psychological assessment situation and when specific memory functioning is in question.

Brain Damage, Chronic↗
PubMed1984

Children's memory for phonemically confusable and nonconfusable letters: changes with age and reading ability.

This experiment focused on differences that occur with age and reading skill in the use of phonemic codes in short-term retention tasks where stimuli were presented visually. In 1 condition, individuals recalled 6-letter strings composed of rhyming and nonrhyming letters after a 15-sec delay under conditions that permitted phonemic coding and rehearsal. 2 other conditions were designed to suppress (a) rehearsal of certain types of phonemic codes in the delay interval and (b) both phonemic coding at stimulus presentation and rehearsal. Subjects were grade 2 average readers matched in reading skill with grade 4 disabled readers, grade 4 average matched with grade 6 disabled, and grade 6 average matched with grade 4 superior readers. Average readers showed a decrease in errors with age in all 3 conditions, although performance was always better in the nonsuppression condition. In the latter, memory for nonrhyming letters was always better than memory for rhyming letters. Differential use of phonemic codes by good and poor readers in grades 4 and 6 was less than that found in previous research with younger children. Finally, by comparing the performances of grade 2 average with grade 4 disabled readers and grade 4 average with grade 6 disabled readers, the developmental lag hypothesis of reading disability was examined. Problems with testing the hypothesis are discussed.

Child↗
PubMed2001

CD4(+)CD7(-) T cells compose the dominant T-cell clone in the peripheral blood of patients with Sézary syndrome.

BACKGROUND: Absence of CD7 antigen expression in T cells defines a subset of normal CD4(+) CD45RO(+) CD45RA(-) memory cells and is furthermore observed in Sézary syndrome (SS). OBJECTIVE: Our purpose was to identify circulating T-cell clones in patients with SS and to elucidate whether the dominant T-cell clones express the CD7 antigen. METHODS: Peripheral blood lymphocytes of patients with SS were analyzed by two-color flow cytometry using antibodies to the V beta region of the T cell receptor (TCR) in combination with an antibody to CD7. In addition, T cells were analyzed for TCR-gamma gene rearrangement by polymerase chain reaction (PCR) techniques. RESULTS: Clonal T-cell expansion was detected in 7 patients with SS by immunostaining of the TCR V beta regions. PCR analysis confirmed the presence of dominant T cell clones. Double-immunostaining revealed that in each case cells of the clonal V beta TCR rearrangement homogeneously express the CD4(+)CD7(-) phenotype. Furthermore, CD4(+)CD7(-) cells express the CD15s antigen but lack expression of CD26 and CD49d. CONCLUSION: Expansion of clonal T cells strongly correlates with the expansion of CD4(+)CD7(-) T cells in 7 tested patients with SS. This supports our model that a subset of late differentiated, normal CD4(+)CD7(-) memory T cells may represent the physiologic counterpart of Sézary cells. Monitoring of circulating T cells with the CD4(+)CD7(-)CD15s(+)CD26(-)CD49d(-) phenotype proved to be useful for the identification of clonal T cells in patients with SS.

Aged↗
PubMed1985

Comparison of verbal and nonverbal memory in elderly normal subjects and dementia patients.

A multimodal memory test was devised to investigate the differences between verbal and nonverbal memory in demented and normal older people (65 to 98 years of age). Recognition memory for faces, geometric designs, tactual fabrics, words, and sentences significantly differentiated between the two groups. Verbal memory was better than nonverbal memory in both groups. No differences in subtest profiles were found between groups. Findings suggest that the verbal-nonverbal dimension is of importance to rehabilitation programs. The relatively slow deterioration of verbal memory with age leads to the suggestion that verbal memory might be capitalized on for the creation of compensatory mechanisms. The similarity in subtest profiles is in agreement with the accelerated aging hypothesis of dementia.

Adult↗
PubMed1978

Optimal strategies in immunology. II. B memory cell production.

After a first encounter with most antigens, the immune system responds to susequent encounters with a faster, more efficient and more strenuous antibody response. The memory of previous antigen contacts is carried by lymphocytes. Expanding on the model developed in Part 1 of this paper, we examine the optimal strategy available to the immune system for B memory cell production. We again find that the strategy should be of the bang-bang variety. The model we consider assumes that antigen triggers a subpopulation of B-lymphocytes. These triggered lymphocytes can proliferate and secrete modest amounts of antibody, or differentiate into non-dividing plasma cells which secrete large amounts of antibody, or differentiate into non-antibody secreting memory cells. Given injections of antigen at two widely spaced times we compute the strategy which minimizes a linear combination of the primary and secondary response times. We find that for all biologically reasonable parameter values the best strategies are ones in which memory cells are produced at the end of the primary response. Exerimental results which bear on the actual strategies employed are discussed.

Antibody Formation↗
PubMed2005

Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style.

BACKGROUND: In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response. METHODS: We studied two groups (n=14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5' variable number tandem repeat (VNTR) polymorphism in the serotonin transporter. RESULTS: The fMRI results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups. CONCLUSIONS: The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information.

Adult↗
PubMed2001

Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory.

Emerging evidence indicates that CD8+ and CD4+ T-cell immunity is differentially regulated. Here we have delineated differences and commonalities among antiviral T-cell responses by enumeration and functional profiling of eight specific CD8+ and CD4+ T-cell populations during primary, memory and recall responses. A high degree of coordinate regulation among all specific T-cell populations stood out against an approximately 20-fold lower peak expansion and prolonged contraction phase of specific CD4+ T-cell populations. Surprisingly, although CD8+ T-cell memory was stably maintained for life, levels of specific CD4+ memory T cells gradually declined. However, this decay, which seemed to result from less efficient rescue from apoptosis, did not affect functionality of surviving virus-specific CD4+ T cells. Our results indicate that CD4+ T-cell memory might become limiting under physiological conditions and that conditions precipitating CD4+ T-cell loss might compromise protective immunity even in the presence of unimpaired CD8+ T-cell responses.

Amino Acid Sequence↗
PubMedDate not supplied

Conceptual background to vascular cognitive impairment.

The current criteria for vascular dementia use a paradigm that first diagnoses dementia on the basis of Alzheimer-type criteria and then superimposes upon this vascular events and risk factors to convert a diagnosis of Alzheimer disease to one of vascular dementia. There are two fundamental flaws with this approach. First, the neuropsychological features of Alzheimer disease are not the same as those for vascular dementia and so use of the current criteria will fail to diagnose many cases, particularly those in whom memory loss is not prominent. Second, progression of vascular dementia should be modifiable by adjustment of risk factors and, possibly, by the use of neuroprotective agents. Given this, it is absurd to wait until patients are frankly demented. It is far more appropriate to detect patients at risk of developing cognitive loss as soon as possible. This could be in the earliest symptomatic stage (vascular cognitive impairment) or even prior to this (brain-at-risk) stage. New criteria, based on evidence rather than on supposition, that focus on early disease are urgently needed.

Alzheimer Disease↗
PubMed1983

Validation of a short Orientation-Memory-Concentration Test of cognitive impairment.

A 6-item Orientation-Memory-Concentration Test has been validated as a measure of cognitive impairment. This test predicted the scores on a validated 26-item mental status questionnaire of two patient groups in a skilled nursing home, patients in a health-related facility, and in a senior citizens' center. There was a positive correlation between scores on the 6-item test and plaque counts obtained from the cerebral cortex of 38 subjects at autopsy. This test, which is easily administered by a nonphysician, has been shown to discriminate among mild, moderate, and severe cognitive deficits.

Aged↗
PubMed1995

Human naive T cells activated by cytokines differentiate into a split phenotype with functional features intermediate between naive and memory T cells.

We have recently shown that CD45RA+CD4+ naive T cells can be activated to proliferate by a combination of IL-2, TNF-alpha and IL-6, but, at variance with TCR-mediated activation, they do not acquire the CD45RO molecule. This prompted us to investigate the phenotype of these cells and the functional features they display upon TCR stimulation. Naive T cells expanded by cytokines, though remaining CD45RA+, express a variety of activation and adhesion molecules which are peculiar to effector or memory T cells. Naive cells primed by cytokines, when activated with anti-CD3 mAb, produce a broad spectrum of cytokines, express CD40 ligand, but are unable to help B cells for Ig synthesis. A subset of CD4+CD45RA+RO-T cells with a phenotype (HLA-DR-, VLA-2+ or IL-2R+) similar to that of cells activated by cytokines in vitro can be found in vivo. These results demonstrate that activation signals delivered by cytokines, in the absence of TCR stimulation, can activate naive T cells to proliferate and differentiate into a 'split phenotype' with elements common to both naive and memory T cells. This novel antigen-independent activation may help to maintain the naive T cell repertoire and facilitate the antigen-responsiveness of naive T cells.

Adult↗
PubMed2007

Mild cognitive impairment: current research and clinical implications.

Mild cognitive impairment refers to the transitional state between the cognitive changes of normal aging and the fully developed clinical features of dementia. This topic has received a great deal of attention in the literature in recent years and is being proposed for clinical applications as well. Clinical guidelines, including the original memory-focused criteria and the more recent broadly defined set of criteria, will be presented. The clinical outcome of individuals with mild cognitive impairment will be discussed and several explanations for variability in the literature will be considered. Predictors of progression, including genetic, neuroimaging, biomarker, and clinical characteristics, will be presented, as will the controversies regarding the underlying neuropathology of mild cognitive impairment. The recently completed mild cognitive impairment clinical trials will be discussed and the lessons learned from them translated into recommendations for future investigations. Finally, the clinical utility of mild cognitive impairment, its incorporation into clinical practice, and directions for future research will be proposed.

Aging↗