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Results for “memory differentiation”

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PubMedDate not supplied

CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated antigens provided by HPV 16 E7.

OBJECTIVE: In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. MATERIAL AND METHODS: Flow-cytometric cell sorted CD8+CD45RA+CD28- and CD8+CD45RA+CD28-T-cells were obtained from patients with cervical cancer and tested for recognition of HLA-A2 restricted peptides derived from the human papillomavirus (HPV)16-E7 gene product using ELISA. HPV DNA in tumor tissue was detected by PCR. RESULTS: We show that the effector CD8+CD45RA+CD28-T-cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with cervical cancer, but also in PBL from patients with an acute mycobacterial infection. CD8+T-cells from 3/6 cancer patients showed a peptide-specific immune response which could be segregated in peptide epitopes which elicited either a strong TNF-alpha production, or GM-CSF and IL-2 secretion. Peptide-reactivity could exclusively be detected in the ex vivo freshly isolated CD8+CD45RA+CD28-T-cell population. A similar situation was found to be true for HLA-A2 presented peptide epitopes derived from M. tuberculosis-associated antigens presented to T-cells obtained from patients with tuberculosis. CONCLUSIONS: The sorting of CD8+CD45RA+CD28-T-cells enables to determine the fine specificity of CD8+ effector T-cells without the need for in vitro manipulation and aids to define the most appropriate target epitopes for novel vaccine designs.

Amino Acid Sequence↗
PubMed2005

Epigenetic memory of active gene transcription is inherited through somatic cell nuclear transfer.

The transplantation of somatic cell nuclei to enucleated eggs has shown that genes can be reprogrammed to an embryonic pattern of expression, thereby indicating a reversal of their epigenetic state. However, in Xenopus nuclear transfer experiments using both endoderm and neuroectoderm donor cells, we have observed substantial overexpression of donor cell type-specific genes, both spatially and temporally, in the wrong cell type in some nuclear transplant embryos. For example, more than half of the embryos prepared from transplanted neuroectoderm nuclei overexpressed the neuroectodermal marker gene Sox2 to an excessive level in their endoderm cells. Because, in Xenopus, there is no transcription for the first 12 cell cycles, some somatic cell nuclei must remember a developmentally activated gene state and transmit this to their mitotic progeny in the absence of the conditions that induced that state. We also find that donor cell-specific genes are transcribed at an earlier stage than normal in an inappropriate cell type. This phenomenon of epigenetic memory applies to genes that are transcribed in donor nuclei; it does not influence those genes that are competent to be transcribed in nuclear transplant embryo tissue, but were not actually transcribed in donor nuclei at the time of nuclear transfer. We conclude that an epigenetic memory is established in differentiating somatic cells and applies to genes that are in a transcriptionally active state.

Animals↗
PubMed2001

Requirement of two NFATc4 transactivation domains for CBP potentiation.

Recruitment of the coactivator CREB-binding protein (CBP) to transcription factors is important for gene expression. Various regions of CBP such as the KIX and CH3 domains have been shown to interact with numerous transcription factors. The NFAT group of transcription factors is involved in multiple biological processes. NFATc4/NFAT3 has been proposed to play an important role in heart hypertrophy, adipocyte differentiation, and learning and memory. We demonstrate here that two transactivation domains, located at the NH(2) and COOH termini of NFATc4, are critical for interacting with CBP. Each transactivation domain interacts with a distinct region of the CBP protein (the KIX and CH3 domains). Binding of CBP potentiates NFATc4-mediated transcription activity. Both transactivation domains of NFATc4 are required for CBP function. Removal of either NFATc4 transactivation domain abolishes CBP potentiation. Conversely, mutation of the KIX or CH3 domain prevents CBP-mediated potentiation of NFATc4 transcription activation. These data demonstrate that formation of a functional NFATc4.CBP transcription complex requires interactions at two distinct sites.

Binding Sites↗
PubMed1989

Dementia in the elderly.

When are confusion and forgetfulness transient signs of normal aging, when are they signs of depression or a medical illness, and when are they signs of dementia? The authors describe clinical features and diagnostic studies that help establish the presence of dementia and discuss ways of coping with both remediable and less treatable types.

Aged↗
PubMedDate not supplied

Source monitoring and false recollection: a life span developmental perspective.

In a variation of Deese's (1959, Journal of Experimental Psychology, 58, 17-22) list-learning paradigm, 32 first-graders, 32 younger adults, and 24 older adults self-generated words that were semantically related to study items prior to recall. This manipulation increased false recollection for children and older adults, but not for younger adults. These data suggest that source-monitoring deficits underlie children's and older adults' illusory memories within the list-learning format. The differential roles played by source monitoring versus declarative memory in the production of false memories are discussed from a life span developmental perspective.

Adult↗
PubMedDate not supplied

Capacity for decision-making in Alzheimer's disease: selfhood, positioning and semiotic people.

The aim of this article is to explore some of the ethical issues surrounding the assessment and determination of capacity of people with dementia in light of their meaning-making ability as shown through discourse. Discourse analysis, two illustrative cases, social construction theory and positioning are used to highlight some of the ethical dilemmas involved in basing a determination of capacity on the diagnosis of dementia and neuropsychological tests of cognitive function. Although neuropsychological tests have their place in assessing some aspects of cognitive function, aspects cognition such as meaning-making ability and selfhood cannot be assessed in a standard format. In dementia, there can be a differential impairment of recall memory while the personality, values and substantial long-term memory remain intact, as does implicit memory for recent events. People with dementia are vulnerable to being negatively positioned, thereby unfairly undermining their rights to make decisions about aspects of their lives. Assessing the capacity of a person with dementia to engage in decision-making is presently in need of examination so as to take into account the person's meaning-making ability and selfhood. Incorrect negative positioning, based on the diagnosis and defects in recall memory, can obscure intact cognitive abilities that allow a person to make decisions about aspects of living, creating the possibility of lasting harm being inflicted on the person with dementia.

Alzheimer Disease↗
PubMed2006

Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response.

CD8+ T cells only require a brief stimulation with antigen in vitro to divide and differentiate into effector and memory cells upon transfer in vivo. The efficiency of clonal expansion and the functional characteristics of memory cells derived from briefly stimulated cells are poorly defined. We developed a system that allowed us to examine programming entirely in vivo. This was achieved by rapidly killing peptide-pulsed DCs carrying a diphtheria toxin receptor transgene with timed injections of diphtheria toxin without altering the course of an accompanying infection. The magnitude of clonal expansion, but not the functionality of the effector cells, correlated directly with the duration of antigen exposure. Furthermore, memory T cells were capable of mounting a secondary response, regardless of the length of antigen encounter during the primary response. These results indicate that the duration of initial antigen encounter influences the magnitude of the primary response, but does not program responsiveness during the secondary challenge.

Adoptive Transfer↗
PubMed1996

Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval.

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the experimental condition. Outside this interval, the ratio was 50:50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Adult↗
PubMed2000

Delay activity of orbital and lateral prefrontal neurons of the monkey varying with different rewards.

We examined neuronal activity in the orbitofrontal cortex (OFC) in relation to reward expectancy and compared findings with those of the lateral prefrontal cortex (LPFC) in the monkey. Activity of OFC neurons was examined in a delayed reaction time task where every four trials constituted one block within which three kinds of rewards and no reward were delivered in a fixed order. More than half of OFC delay neurons were related to the expectancy of delivery or nodelivery of a reward as the response outcome, while some neurons showed nature-of-reward-specific anticipatory activity changes. These delay-related activities reflected the preference of the animal for each kind of reward and were modulated by the motivational state of the animal. LPFC neurons are reported to show nature-ofreward-specific anticipatory activity changes in a delayed response task when several different kinds of rewards are used. Such rewarddependent activity is observed in LPFC delay neurons both with and without spatially differential delay (working memory-related) activity. Although reward expectancy-related activity is commonly observed in both OFC and LPFC, it is suggested that the OFC is more concerned with motivational aspects, while the LPFC is related to both the cognitive and motivational aspects of the expectancy of response outcome.

Animal Feed↗
PubMed1998

CD45RA(bright)/CD11a(bright) CD8+ T cells: effector T cells.

An important aspect of peripheral T cell development is the differentiation from naive into memory cells. To distinguish naive from memory cells, CD45RA and CD11a are commonly used: CD45RA+ or CD11a(dim) T cells are regarded as naive, while CD45RA- or CD11a(bright) T cells are thought to be of memory type. There is, however, a CD8+ T cell subset which is CD45RA+ and at the same time CD11a(bright). It increases with age and in patients with systemic viral infections, though its functional role in the immune response is unknown. In the present study, we give evidence that this subset is related to memory-like T cells as it produces IFN-gamma and tumor necrosis factor-alpha, contains high levels of perforin, and expresses CD95 in the same way as memory-type CD45RA-/CD11a(bright) CD8+ T cells. Since it contains a high percentage of CD28- and CD57+ cells, is increased in size and granularity, and is transiently expressed following in vitro stimulation of naive CD8+ T cells, we speculate that this subset mainly represents recently activated effector T cells that are able to interact with CD80 and CD86 (B7-1 and B7-2 respectively) negative tissue cells.

Adult↗
PubMed2003

Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells.

Previous studies have suggested that defective immune responses in early life may be related to the immaturity of neonatal antigen-presenting cells. To test this hypothesis, we assessed the capacity of neonatal dendritic cells (DC) to prime and polarize in vitro human naive antigen-specific T cells. We report that mature cord blood DC efficiently prime an oligoclonal population of antigen-specific CD8 T cells, capable of cytolytic activity and IFN-gamma secretion. In contrast, cells primed by immature cord blood DC do not acquire cytolytic activity and secrete lower amounts of IFN-gamma. Upon priming by either immature or mature DC, neonatal T cells acquire markers of activation and differentiation towards effector-memory cells. Our results demonstrate that, if appropriately activated, neonatal DC can prime efficient cytotoxic T lymphocyte (CTL) responses. Furthermore, these findings have important implications for the development of vaccine strategies in early life and for the reconstitution of a functional CTL repertoire after bone marrow transplantation.

Antigen-Presenting Cells↗
PubMed2003

New interleukins: are there any more?

PURPOSE OF REVIEW: It is now well established that cytokines play a critical role in the regulation of the immune system. Processes such as lymphoid development, differentiation, homeostasis, tolerance and memory are all regulated by cytokines that bind the type I family of cytokine receptors. Like the interferons, which bind receptors designated as the type II cytokine receptor family, type I cytokines also have essential functions in host defence. RECENT FINDINGS: Recently, a number of new interleukins and their receptors have been discovered and their role in mounting an appropriate immune response is currently being studied. In this review we will describe the new interleukin-12 family of cytokines, which now includes two other members: interleukins 23 and 27. We will also review the newly discovered interleukins 28 and 29, also known as interferon-lambdas, which bind to the type II family of cytokine receptors, their structure and the structure of their receptors, their biological activities and modes of signalling. SUMMARY: These new molecules will certainly be the focus of active research in the immediate future. Their discovery opens the door to new therapeutic approaches to the treatment of various diseases ranging from infections from intracellular pathogens to viral infections.

Humans↗
PubMed1987

Processing of critical information by physicians and medical students.

In the study reported here, differences between physicians and medical students in their recall of information from clinical problems were investigated. The focus of the study was on the recognition and recall of critical cues within cases as a function of problem difficulty and the organization of clinical information. Two clinical cases in two structural forms (typical and random) were designed, and the participants' written recall of the cases was analyzed using the techniques of discourse analysis. The results show that the physicians recalled significantly more critical cues than the medical students. However, when the case had a temporally ordered, underlying disease process, the random structure of the text disrupted both the physicians' ability to recall critical cues and the accuracy of their diagnoses. The medical students were unaffected by problem type or structural form in the amount of information they recalled. The results show that the physicians and medical students formulate the information from clinical problems differently, and this difference is due to the fact that the physicians recognize patterns of familiar problems with respect to critical cues but the students do not.

Clinical Competence↗
PubMed1991

Comparison of computerized and examiner-administered neurobehavioral testing techniques.

To better understand the relationship of newly developed computerized neurobehavioral tests to their examiner-administered counterparts, performance on four pairs of tests was compared among 185 solvent-exposed workers in the paint manufacturing industry. Two approaches to the comparison of the test methods (computer or examiner) were employed: (1) the multitrait-multimethod correlation matrix and (2) linear regression modeling of the difference scores between pairs of tests (same functional domain, different test formats). The data revealed that the validity criteria of the multitrait-multimethod technique were met for the tests of simple visual reaction time and attention-concentration (digit symbol substitution). Linear regression analyses demonstrated that the digit symbol substitution and visual memory test pairs were differentially affected by age, vocabulary, solvent exposure, or manual dexterity. Overall, this latter approach holds promise as a means of understanding test format similarities and differences.

Adult↗
PubMed1987

Differential effects of the anxiolytic drugs, diazepam and buspirone, on memory function.

The effects of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) were studied in comparison with placebo on memory function in 39 subjects diagnosed with generalized anxiety disorder. Neither drug altered the immediate recall of a list of 16 nouns or impaired digit span, a second test of immediate memory. Diazepam selectively impaired the recall of nouns after a 20 min delay when compared with placebo. In contrast, neither dose of buspirone altered the delayed recall of the word list. The implications of such different effects of anxiolytic drugs on memory function for the clinical treatment of anxiety are discussed.

Anti-Anxiety Agents↗
PubMed1980

Antigen-initiated B-lymphocyte differentiation. XVII. The inhibitory effects of recent antigen prepriming on the subsequent responsiveness of 'pre-progenitor' B cells.

We have analysed the transient unresponsiveness of B cells following specific antigen prepriming. The effect is restricted to adoptive-transfer antibody-forming cell (AFC) progenitors (that is, 'pre-progenitors') and does not occur with the separate subset of cell culture AFC progenitors ('direct progenitors'). The transient unresponsiveness is displayed by both primary and secondary 'pre-progenitor' B cells. Mixing experiments and experiments with athymic mice indicate that the effect is not due to suppressor T cells or other inhibitory cells. Nor is the effect due to an impaired seeding ability of the activated or antigen-binding cells, since after adoptive transfer the preprimed cells can be activated by an appropriate non-specific stimulus. The most likely explanation involves direct interaction of specific antigen with the antigen receptors on 'pre-progenitor' B cells, rendering these cells more prone to temporary or permanent 'tolerance' on further antigen contact or, alternatively, directing their differentiation away from IgM AFC production on day 8 after transfer.

Adoptive Transfer↗
PubMed1977

Measuring dementia.

Maudsley Tests of the Sensorium (used by clinicians to assess verbal memory and orientation) and Kendal's Memory for Design (used by psychologist to assess visual memory) were employed to differentiate between elderly patients with organic brain damage (neurologic disease, chiefly stroke) and those with functional psychiatric disorders which had been present in youth. There were 25 patients in each group. Both test differentiated organic from functional disorders. There was no statistically significant difference in the effectiveness of the two tests.

Brain Diseases↗
PubMed2002

Observing mother-child relationships across generations: boundary patterns, attachment, and the transmission of caregiving.

Grounded in both attachment and family systems theories, this study is one of the first to examine how relationship patterns observed in mothers' current relationships with their own mothers are recreated in their relationships with their infants. Mostly white, middle-class families (N = 55), including maternal grandmothers, mothers, and infants, were observed when infants were 6, 9, and 18 months old. At 6 months, mothers and grandmothers completed self-report assessments and worked together on discussion tasks. These interactions were coded using the Boundary Assessment Coding System, developed for the present study, which assessed three relational patterns: disengagement, balance, and entanglement. At 9 months, mothers were rated on sensitivity and intrusiveness while playing with and feeding their infants; and, at 18 months, infant-mother attachment was assessed using the Strange Situation. Multiple regression analyses revealed, as predicted, that mothers who remembered being accepted by their mothers as children and who were in highly balanced relationships with their own mothers currently were more sensitive and less intrusive with their 9-month-old infants. Further, discriminant function analyses indicated that memories of acceptance, high levels of balance, and low levels of disengagement differentiated secure from insecure attachment, whereas memories of overprotection and high levels of entanglement distinguished resistant from secure and avoidant attachment. Discussion focuses on the theoretical hypothesis that mothers internalize relationship strategies experienced with their own caregivers and recreate these patterns with their infants.

Adult↗