Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “memory differentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1995

Reduced frequency of memory CD8+ T lymphocytes in cerebrospinal fluid and blood of patients with multiple sclerosis.

Three color flow cytometry was used to analyze immunoregulatory lymphocyte subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) of 21 patients with multiple sclerosis (MS) and 15 age-matched healthy control subjects. Two cell surface antigens associated with T lymphocyte memory and activation, CD45R0 and CD29, were analyzed on the CD4+ and CD8+ subpopulations, respectively. A selective decrease in the expression of the CD45R0 isoform among CD8+ cells was noted in both PB (p < 0.005) and CSF (p > 0.0001) of patients with MS as compared with the control group while the expression of CD29 did not differ between the groups. These changes could indicate a defective differentiation into mature memory CD8+ T lymphocytes in patients with MS. Furthermore, the CD3+CD16/56+ T lymphocyte subset capable of mediating NK cell-like activities was investigated. Although this cell population is quantitatively small, a significant reduction of the proportion of this cell type was detected in both BP and CSF of the MS group compared with the controls (p < 0.01 and p > 0.001, respectively). Further studies are needed to establish the role of these observations in the pathogenesis of MS.

Adult↗
PubMed2001

Perpetuation of immunological memory: a relay hypothesis.

A mechanism is proposed which explains the perpetuation of B-cell immunological memory indefinitely without requiring the presence of long-living memory cells or persisting antigen. The salient feature of this model is that immunological memory can be perpetuated indefinitely through the mutual interaction of idiotypic and anti-idiotypic B cells. These cells mutually stimulate and clonally expand with either specific or bystander T-cell help. Because B cells can present antigen, they present 'apparently foreign' idiopeptides to T cells. The idiopeptides of de novo synthesized antibody is presented to CD8+ T cells that recognize the idiopeptide-presenting cell as targets and regulate their population. The recycling of immunoglobulins from surface to endosomal compartment of B cells leads to the presentation of idiopeptides by major histocompatibility complex (MHC) class II to CD4+ T cells. Even if the majority of the clonally expanded cells die because of lack of stimulation, cytotoxic T lymphocyte (CTL) lysis or for other reasons, the surviving cells will be able to carry forward the memory. This mechanism also provides a means for affinity maturation through idiotypic selection of somatically mutated high affinity cells or those from the naïve pool. We have termed these two types of complementary B cells as Burnet B cells: those which recognize the antigen or antigen mimic, and Jerne B cells, which can recognize the idiotypes of antibody and carry antigen mimics. The proposed hypothesis can explain differential duration of memory for different antigens, the shelf space paradox, affinity maturation, repertoire shift, etc.

Animals↗
PubMed2006

Epigenetic memory loss in aging oligodendrocytes in the corpus callosum.

In this study, we address the hypothesis that aging modifies the intrinsic properties of oligodendrocytes, the myelin-forming cells of the brain. According to our model, an "epigenetic memory" is stored in the chromatin of the oligodendrocyte lineage cells and is responsible for the maintenance of a mature phenotype, characterized by low levels of expression of transcriptional inhibitors. We report here an age-related decline of histone deacetylation and methylation, the molecular mechanisms responsible for the establishment and maintenance of this "epigenetic memory" of the differentiated state. We further show that lack of histone methylation and increased acetylation in mature oligodendrocytes are associated with global changes in gene expression, that include the re-expression of bHLH inhibitors (i.e. Hes5 and Id4) and precursor markers (i.e. Sox2). These changes characteristic of the "aging" oligodendrocytes can be recapitulated in vitro, by treating primary oligodendrocyte cultures with histone deacetylase inhibitors. Thus, we conclude that the "epigenetic memory loss" detected in white matter tracts of older mice induces global changes of gene expression that modify the intrinsic properties of aged oligodendrocytes and may functionally modulate the responsiveness of these cells to external stimuli.

Age Factors↗
PubMed2005

Planning and realisation of complex intentions in patients with Parkinson's disease.

BACKGROUND: There is some evidence that patients with Parkinson's disease may impaired in prospective memory performance (planning and self initiated realisation of delayed intentions). Little is known about the effect of the disease on distinct phases of prospective memory and the potential mechanisms underlying these effects. OBJECTIVE: To investigate intention formation, intention retention, intention initiation, and intention execution of patients with Parkinson's disease and test for the mediating influence of working memory, inhibition, short term retrospective memory, and divided attention. METHODS: 16 patients with Parkinson's disease and 16 age and education matched normal controls were given a complex event based prospective memory task which differentiates four phases of prospective remembering. In addition, participants completed tasks assessing potential cognitive mediators. RESULTS: On the prospective remembering task, Parkinson patients were impaired in the intention formation phase and showed a trend towards impairment in the intention initiation. In contrast, there were no impairments of retrospective intention retention or the fidelity with which the patients executed their previously developed plan. The group effects were related to interindividual differences in working memory span. CONCLUSIONS: The results suggest that the planning phase of prospective remembering is specifically impaired in Parkinson's disease, and that the impairment is related to working memory deficit. In contrast, even when complex intentions have to be remembered, the retrospective storage of intentions to be performed is not impaired.

Aged↗
PubMed1992

Excitotoxic lesions of rat basal forebrain: differential effects on choline acetyltransferase in the cortex and amygdala.

Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either alpha-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N-methyl-D-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and alpha-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. alpha-Amine-3-hydroxy-5-methyl-4-isoxazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N-methyl-D-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N-methyl-D-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMedDate not supplied

[The geriatric team in the memory clinic].

The early and differential diagnosis of senile dementia is still a problem. The work of a multiprofessional team in the Memory Clinic Essen is reviewed. the combination of qualifications of the team corresponds with the diagnostic algorithms of DMS-III R and ICD 10. Members of the team are a geriatrician, a psychiatrist, a geragoque, and a psychologist. Every specialist examines the patient using his specialized method. The results are discussed in a diagnostic conference. Out of the different methods and views of the specialists a comprehensive image of the patient takes shape and allows a better understanding of the dementia.

Aged↗
PubMed1993

Bovine gamma/delta T cells bind E-selectin via a novel glycoprotein receptor: first characterization of a lymphocyte/E-selectin interaction in an animal model.

E-Selectin is an inducible adhesion protein expressed by endothelial cells and recognized by leukocytes during their extravasation from the blood into inflamed tissues. Originally, E-selectin was defined as a myeloid cell-specific adhesion protein, but recent studies have shown it to be recognized by human lymphocytes as well. These lymphocytes represent a memory T cell subset and have been shown to express the HECA-452 carbohydrate epitope (CLA+ lymphocytes). We extend these findings and show that ruminant gamma/delta T cells bind E-selectin as well; and we provide preliminary evidence that this interaction is mediated by a novel glycoprotein receptor on the lymphocyte. Unlike conventional T cells (alpha/beta T cells), gamma/delta T cells from neonatal and mature animals bind E-selectin, suggesting that prior antigen stimulation and differentiation to a memory lymphocyte are not required for this interaction. Neuraminidase treatment of the gamma/delta T cells or addition of ethylenediaminetetraacetic acid (EDTA) to the assay abrogates binding, demonstrating the importance of sialic acid and divalent cations, which is consistent with other E-selectin-mediated adhesion events. However, previously defined E-selectin carbohydrate ligands, such as sialyl Lewis x on neutrophils and the HECA-452 epitope on human memory lymphocytes, are antigenically different than the carbohydrates on ruminant gamma/delta T cells since the mAbs CSLEX and HECA-452 do not recognize these cells. Protease treatment of gamma/delta T cells significantly inhibits their binding to E-selectin; however, previously characterized adhesion glycoproteins, such as L-selectin, CD44, and CD18, are not involved in the adhesive event. An E-selectin affinity column purifies a single glycoprotein of 250 kD (280 kD under reducing conditions) from gamma/delta T cell detergent lysates. Neuraminidase digestion of the 250-kD product as well as EDTA abolishes binding to E-selectin. Finally, E-selectin expression in vivo appears to mediate gamma/delta T cell accumulation. Stimulation of bovine skin with tumor necrosis factor alpha induced an increase in E-selectin expression that was associated with an influx of gamma/delta T cells at the same site.

Animals↗
PubMed1989

Hemispheric asymmetry in tactile forgetting induced by tactually-guided movement.

Asymmetries in tactile short-term memory related to differential specialization of the cerebral hemispheres were studied in normal human adults using the Brown-Peterson distractor task. When the distractor was an auditory arithmetic task, no difference emerged between the two hands for the retention of touches to the fingers; however, when the distractor was a tactual maze task executed by the right hand, asymmetry in favor of the left hand was observed. Specifically, when the right hand performed the tactual maze, there was greater interference with tactile memory than when the left hand performed the maze, independent of which hand received the memory material. The results support a characterization of short-term memory as embracing multiple, limited storage capacities divided along the lines of processing demands, arising from different classes of material, placed on the two cerebral hemispheres.

Adult↗
PubMed1996

CD4+ memory T cells are the predominant population of HIV-1-infected lymphocytes in neonates and children.

BACKGROUND: CD4+ memory T cells express CD45RO and are the principal viral reservoir in HIV-infected adults. In infants and children, CD45RO T cells comprise the minority of the CD4+ T-cell population. The majority of blood CD4+ T cells are naive, expressing CD45RA. OBJECTIVE: To determine the developmental stage at which pediatric CD4+ T cells become susceptible to HIV-1 infection in vivo by determining which T-cell population harbors HIV-1 proviral DNA. DESIGN: A prospective, cross-sectional analysis of peripheral blood CD8+ T cells, CD45RA, or CD45RO CD4+ T cells obtained from 10 HIV-infected neonates and children were analysed for provirus. METHODS: Semi-quantitative polymerase chain reaction methods were used to detect HIV-1 proviral DNA within purified lymphocyte populations selected using immunoaffinity magnetic microspheres. RESULTS: CD8+ T cells harbored no detectable HIV-1, indicating that infection of common thymocytes does not contribute to the population of infected blood T cells. In five children and two of the five neonates, the CD4+ CD45RO memory T lymphocytes contained 10-100-fold greater numbers of infected cells than the CD4+ CD45RA naive T-cell population. Three neonates, who exhibited rapid disease progression, demonstrated high proviral levels in their CD4+ CD45RA T cells. The normal age-related predominance of CD4+ CD45RA T cells was preserved independent of CD4+ T-cell attrition. CONCLUSIONS: The majority of HIV-1-infected blood CD4+ T cells in infants and children are restricted to the small population of terminally differentiated CD4+ CD45RO memory T cells. Neonates with rapid CD4+ T-cell attrition display high levels of provirus in their CD4+ CD45RA T-cell population.

Adult↗
PubMed2002

Autobiographical memory and emotion in a non-clinical sample of women with and without a reported history of childhood sexual abuse.

OBJECTIVES: This study focused on the relationship between reported CSA history, subsequent autobiographical memory retrieval, intrusive and dysfunctional thoughts, and mood in a non-clinical sample. The main hypothesis was that specificity in autobiographical memory recall would differentiate between women with a reported history of CSA and those without, and that this finding would be independent of current mood. DESIGN: A between-group comparison of women (female undergraduates) with and without a reported history of CSA. Within group correlations were also examined for the reported CSA group. METHOD: Participants were 79 female students, of whom 22 (28%) reported a history of CSA. All participants completed questionnaires requesting information on a history of CSA, a questionnaire version of the autobiographical memory test, the profile of mood states, the dysfunctional attitude scale, and the impact of events scale. RESULTS: The reported CSA group gave significantly fewer specific autobiographical memories, were significantly more anxious, depressed and angry, and held more dysfunctional beliefs than the comparison group. However, specificity of memory was not correlated with the degree of this mood disturbance or with the impact of event scale or extent of dysfunctional beliefs. CONCLUSIONS: Models of the long-term effects of CSA should incorporate the effects CSA may have on subsequent retrieval for memory of non-abuse events. To improve treatment outcome, clinicians may have to directly address these deficits in therapy.

Adolescent↗
PubMed1999

Altered ex vivo balance between CD28+ and CD28- cells within HIV-specific CD8+ T cells of HIV-seropositive patients.

The CD8+CD28- cell population in the blood of HIV-infected individuals is considerably expanded. Yet the cause of this expansion is not clear. The recent demonstration of identical TCR-rearranged genes in CD8+CD28+ and CD8+CD28- expanded T cells of HIV-seropositive patients supports the hypothesis that these two subpopulations are phenotypic variants of the same lineage. To further elucidate the precise relationship between them, we measured the fraction of CD28+ and CD28- T cell subsets in IFN-gamma-producing CD8+ T cells by intracellular staining and cytofluorometry as a functional test for ex vivo recognition of epitopes derived from HIV-1, Epstein-Barr virus (EBV) and influenza virus. HIV-specific CD8+ T cells were predominantly CD28 in all the eight HIV-seropositive subjects tested. In contrast, the anti-EBV and anti-influenza CD8+ T cells were mainly CD28+ in these patients as well as in HIV-seronegative individuals. This supports the notion that the CD8 CD28 hyperlymphocytosis observed in HIV infection is due mainly to chronic activation and differentiation of HIV-specific memory CD8+CD28+ T cells into terminally differentiated CD8+CD28-lymphocytes, because of intense HIV-1 replication and without any important bystander activation. This clarification of the mechanisms underlying the CD8+CD28- expansion in HIV-induced pathogenesis may have important therapeutic implications.

CD28 Antigens↗
PubMed2006

A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination.

Despite major progress in T lymphocyte analysis in melanoma patients, TCR repertoire selection and kinetics in response to tumor Ags remain largely unexplored. In this study, using a novel ex vivo molecular-based approach at the single-cell level, we identified a single, naturally primed T cell clone that dominated the human CD8(+) T cell response to the Melan-A/MART-1 Ag. The dominant clone expressed a high-avidity TCR to cognate tumor Ag, efficiently killed tumor cells, and prevailed in the differentiated effector-memory T lymphocyte compartment. TCR sequencing also revealed that this particular clone arose at least 1 year before vaccination, displayed long-term persistence, and efficient homing to metastases. Remarkably, during concomitant vaccination over 3.5 years, the frequency of the pre-existing clone progressively increased, reaching up to 2.5% of the circulating CD8 pool while its effector functions were enhanced. In parallel, the disease stabilized, but subsequently progressed with loss of Melan-A expression by melanoma cells. Collectively, combined ex vivo analysis of T cell differentiation and clonality revealed for the first time a strong expansion of a tumor Ag-specific human T cell clone, comparable to protective virus-specific T cells. The observed successful boosting by peptide vaccination support further development of immunotherapy by including strategies to overcome immune escape.

Antigen Presentation↗
PubMed2006

The key regulators of adult T helper cell responses, STAT6 and T-bet, are established in early life in mice.

Murine neonatal immunity is typically Th2 biased. This is characterized by high-level IL-4 production at all phases of the immune response and poor IFN-gamma memory responses. The differential expression of Th1/Th2 cytokines by neonates and adults could arise if the critical regulators of Th differentiation and function, STAT6 and T-bet, operate differently during the neonatal period. To test this idea, the Th cell responses of wild-type, T-bet-deficient, or STAT6-deficient mice were compared in vitro and in vivo. The absence of these factors had similar qualitative effects on the development of effector function in neonates and adults, i.e., if a Th lineage was inhibited or enhanced in adult animals, a similar phenomenon was observed in neonates. However, there was a striking difference observed in the in vivo Th1 memory responses of STAT6-deficient mice initially immunized as neonates. Antigen-specific IFN-gamma production was increased 50-100-fold in STAT6-deficient neonates, achieving levels similar to those of STAT6-deficient adults. These findings demonstrate that STAT6 and T-bet signals are central in shaping Th responses in wild-type neonates, as in adult mice, and that the master regulators of Th cell development and function are already firmly established in early life.

Animals↗
PubMed1997

Dissociation between features and feature relations in infant memory: effects of memory load.

Four experiments examined the effects of the number of features and feature relations on learning and long-term memory in infants. Three-month-olds learned to activate a mobile composed of either two or three kinds of blocks that differed in color, the figures displayed on them, and the figures' colors. Twenty-four hours later, infants trained with two objects discriminated feature recombinations but those trained with three objects did not. Even infants trained with three objects discriminated novel features, however, indicating that they remembered the individual features but not the relations among them. A subsequent experiment revealed that this dissociation between features and relations was induced by differential accessibility to memory rather than an encoding failure. We conclude that the size of the memory load selectively constrains infants' long-term memory for relational information. These results suggest that in infancy, as in adulthood, features and relations are psychologically distinct and that memory organization parallels the organization of perceptual processing.

Association Learning↗
PubMed2006

Enhanced memory performance on an internal-internal source monitoring test following acute psychosocial stress.

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe.

Adult↗
PubMed2006

Hippocampal up-regulation of NCAM expression and polysialylation plays a key role on spatial memory.

Memory formation has been associated with structural and functional modifications of synapses. Cell adhesion molecules are prominent modulators of synaptic plasticity. Here, we investigated the involvement of the cell adhesion molecules, NCAM, its polysialylated state (PSA-NCAM) and L1 in spatial learning-induced synaptic remodeling and memory storage. A differential regulation of these adhesion molecules was found in the hippocampus of rats submitted to one training session in the spatial, but not cued, version of the Morris water maze. Twenty-four hours after training, synaptic expression of NCAM and PSA-NCAM was increased, whereas L1 appeared markedly decreased. The regulation of these molecules was spatial learning-specific, except for L1 reduction, which could be attributed to swimming under stressful conditions rather than to learning. Subsequent psychopharmacological experiments were performed to address the functional role of NCAM and PSA-NCAM in the formation of spatial memories. Rats received an intracerebroventricular injection of either a synthetic peptide (C3d) aimed to interfere with NCAM function, or endoneuraminidase, an enzyme that cleaves polysialic acid from NCAM. Both treatments affected acquisition of spatial information and lead to impaired spatial memory abilities, supporting a critical role of the observed learning-induced up-regulation of synaptic NCAM expression and polysialylation on spatial learning and memory. Therefore, our findings highlight NCAM as a learning-modulated molecule critically involved in the hippocampal remodeling processes underlying spatial memory formation.

Animals↗
PubMed2006

Diazepam-induced prospective memory impairment and its relation to retrospective memory, attention, and arousal.

The amnestic effects of benzodiazepines are well documented on a variety of memory tasks. However, prospective memory (PM), or remembering to execute an action at a future time, has not been studied previously. This study examined the effect of diazepam on word list recall, PM, sustained attention, and subjective ratings of arousal. Forty-eight healthy participants, aged 19-35, received an average of 0.19 mg/kg oral diazepam or placebo in a double-blind manner. Retrospective memory and PM were assessed by free recall of unrelated word lists and by instructing participants to request a hidden belonging at the end of the session, respectively. Sustained attention was measured by multiple trials of a digit cancellation task, and subjective arousal was assessed by self-ratings of drowsiness. Diazepam impaired performance on all measures, including PM. Reduced PM performance was associated with decreased subjective arousal in the diazepam group but was unrelated to sustained attention. This is the first report of the effects of benzodiazepines on prospective remembering, and further supports the view that the arousal/attentional system is composed of partially independent subsystems that have differential relationships to memory.

Adult↗
PubMed2000

Functional subsets within clonally expanded CD8(+) memory T cells in elderly humans.

With advancing age, healthy humans frequently demonstrate large clonal expansions of CD8(+) T cells in the peripheral blood, which persist for long periods of time and appear to be maintained as a population of memory cells. We studied nine large T cell clones in five elderly individuals. We noted that in most cases the expanded clones were dominated by cells that did not express CD28, a pivotal molecule in T cell activation, and these clones proliferated poorly in culture. However, nearly all of the clonal expansions had CD28(+) fractions and some of these cells appeared to lose CD28 gene expression with stimulation in culture. CD28(+) cells demonstrated greater proliferation in both bulk and limiting dilution cultures compared to CD28(-) cells bearing the same TCR, whereas CD28(-) cells showed increased perforin expression. Together, these data suggest that loss of CD28 expression marks functional differentiation to cytotoxic memory cells within these clonal expansions and likely within CD8(+) memory populations in general.

Aged↗