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PubMed1980

Innunocytological studies on the constituent cells of the secondary nodules in human tonsils.

The rate of presence of surface immunoglobulins (sIg) and incidence of the surface receptors (SRBC-receptor, Fc-receptor and C3 receptor) were examined on the constituent cells of secondary nodules enucleated from human tonsils and foated in suspension. As most of the rosette-forming cells for SRBC-receptor were judged to belong to small round cells, the germinal center was considered to be a "non-T-cell region." The coronal B-lymphocytes and small germinal center cells were fairly matured B-cells because both bore sIg (100%), Fc receptor (25%) and C3 receptor (90-80%), while the former cells were thought to be more matured on the basis of their possession of surface delta-chain. As the large germinal center cells bore sIg (50%) and carried Fc receptor (25%) and C3 receptor (50%), they seemed to be the major immature cells among the cell constituents of the secondary nodules. Moreover, it is presumed that the majority of the large germinal center cells are able to differentiate into coronal B-lymphocytes, probably memory cells, and a minor population of them into cIg-containing cells.

B-Lymphocytes↗
PubMed2004

Time perception: does it distinguish ADHD and RD children in a clinical sample?

This study used a double-dissociation design to evaluate whether children with ADHD demonstrated specific deficits relative to children with Reading Disorders. Recent theory suggests that ADHD children have deficits in time perception and working memory, whereas RD children have deficits in phonological decoding. The performance of 113 clinic-referred children aged 6-11 was examined using measures of working memory, phonological processing, and time perception. Respondents completed two time production tasks in which they were to judge when 30-s had elapsed, and another in which they were asked to estimate the duration of the Conners' CPT (CCPT). Time Perception and phonological processing variables were submitted to a 2 x 2 ANCOVA (ADHD vs. RD), covarying for age, SES, IQ, and working memory. Children with ADHD were more likely to overestimate the time taken for the CCPT than children without ADHD, but no group differences were found on the 30-s estimation tasks. Children with RD did not display deficits in time estimation, but showed deficits in auditory phonological processing. The lack of interaction effects supported an "etiological subtype" over the "phenocopy" model of ADHD and RD. No group differences were detected using the CCPT. Although our previous studies did not find an order effect for the Conners' CPT in a 1-hr battery, a fatigue effect was evident with a 1.5-hr battery. The implications for Barkley's behavioral inhibition theories (R. Barkley, 1997) are discussed.

Articulation Disorders↗
PubMed1998

c-Rel is essential for B lymphocyte survival and cell cycle progression.

c-Rel is a lymphoid-specific member of the NF-kappaB/Rel family of transcriptional factors. To investigate the role of c-Rel in B lymphocyte function, we generated a c-Rel(-/-) mouse via a gene targeting approach. Although early lymphocyte development is normal in c-Rel(-/-) mice, there are significantly fewer B cells displaying a memory (IgM/IgD-) phenotype. Upon immunization, c-Rel(-/-) mice generate fewer B cells with a germinal center (PNAhi) phenotype. In vitro, c-Rel(-/-) B cells proliferate poorly upon ligation of their surface IgM or CD40 receptors or when stimulated with either lipopolysaccharide (LPS) or T cell help. Early molecular events that precede proliferation, such as increases in RNA synthesis as well as IL-2 receptor alpha chain expression, are greatly diminished in c-Rel(-/-) B cells. Furthermore, c-Rel(-/-) B cells are impaired in the ability to receive survival signals generated by anti-IgM or LPS. In contrast, CD40-mediated cell survival is normal in c-Rel(-/-) B cells, suggesting the involvement of a survival-signaling pathway that is independent of c-Rel. When c-Rel (-/-) B cells are co-stimulated with either anti-IgM and CD40 or LPS and CD40, they are rendered capable of progressing through the cell cycle. Finally, co-culture experiments suggest that the defects observed in c-Rel(-/-) B cells are intrinsic to the cell and can not be rescued through either cell-cell contact or addition of soluble factors. Thus, c-Rel is requisite for differentiation to the germinal center and memory B cells in vivo and is required for the transduction of survival and cell cycle progression signals mediated by anti-IgM and LPS in vitro. Furthermore, while c-Rel is involved in CD40-induced proliferation, it is apparently dispensable for the survival signals transduced by CD40.

Animals↗
PubMed2002

Different trends in modulation of NMDAR1 and NMDAR2B gene expression in cultured cortical and hippocampal neurons after lead exposure.

Exposure to heavy metal lead (Pb(2+)) has been reported to cause problems in cognitive functions of the brain, e.g. memory loss and difficulties in mental development. N-Methyl-D-aspartate receptors (NRs) are important molecules that are known to be involved in mediation of learning and memory. In order to investigate the effects of Pb(2+) on the gene expression of NR1 and NR2B subunits in neurons, primary cell cultures of rat cortical and hippocampal neurons were employed. After treatments with different concentrations of Pb(2+) ions in culture medium (0, 5, 10, 25 and 50 microM), the cellular localization of Pb(2+) in neurons was evaluated by laser scan confocal microscopy by using a Pb(2+) ion specific fluorescence probe. In addition, the gene expression of NR1 and NR2B subunits was determined by reverse transcriptase-polymerase chain reaction, immunofluorescence and Western blotting. The results of the present study showed that both cortical and hippocampal neurons accumulated intracellular Pb(2+) in accordance with the concentrations of Pb(2+) ions present in the culture medium. After Pb(2+) treatments, levels of NR1 mRNA, immunoreactivity and protein were found to be unchanged but levels of NR2B mRNA, immunoreactivity and protein were found to be significantly increased in cortical neurons. In contrast, both NR1 and NR2B mRNAs, immunoreactivity and proteins were found to be significantly decreased in hippocampal neurons. The changes in gene expression were found to be dose dependent in accordance with the Pb(2+) concentrations. The present results indicate that Pb(2+) has a differential effect on the expression of NR1 and NR2B subunits in cortical and hippocampal neurons, respectively. It is likely that the toxic effects of Pb(2+) may cause differential damage to different types of memory that are mediated by cortical and hippocampal neurons, respectively.

Animals↗
PubMed2002

Distribution and functional analysis of memory antiviral CD8 T cell responses in HIV-1 and cytomegalovirus infections.

In the present study, we have investigated the anatomic distribution and the function of different populations of HIV-1- and cytomegalovirus (CMV)-specific memory CD8 T cells. The different populations of virus-specific memory CD8 T cells were distinguished on the basis of the expression of CD45RA and CCR7, and the composition of HIV-1- and CMV-specific memory CD8 T cell pools were compared in subjects with chronic HIV-1 and CMV co-infection. The distribution of HIV-1-specific CD8 T cells was similar between blood and lymph node. However, CMV-specific CD8 T cells were accumulated predominantly in the blood away from the lymphoid tissue. The majority (>70%) of HIV-1- and CMV-specific CD8 T cells in both blood and lymph node had a phenotype, e.g. CCR7-, typical of effector T cells. HIV-1-specific memory CD8 T cells were mostly (>80%) pre-terminally differentiated cells, e.g. CD45RA-CCR7-, in both blood and lymph node while 30-50% of CMV-specific CD8 T cells were terminally differentiated, e.g. CD45RA+CCR7-. Therefore, consistently with studies in mice, antigen-specific effector memory CD8 T cells accumulate predominantly in the target organ of the pathogen in humans, and the differences in the composition of HIV-1- and CMV-specific CD8 T cell pools were also present in the lymphoid tissue. A substantial proportion (30-40%) of virus-specific CD8+CCR7+ T cells produced IFN-gamma. Thus, indicating that the expression of CCR7 does not provide a clear-cut separation of memory CD8 T cells with distinct functional capacities. Taken together, these results provide further advances in the characterization of human memory CD8 T cells.

Adult↗
PubMed2002

Decline in verbal memory during preclinical Alzheimer's disease: examination of the effect of APOE genotype.

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-epsilon4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE epsilon4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale-Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-epsilon4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD.

Aged↗
PubMed2002

Working memory of action: a comparative study of ability to selecting response based on previous action in New World monkeys (Saimiri sciureus and Callithrix jacchus).

Working memory of the outcome of one's own action is important for organizing and learning appropriate behaviors in a given condition. To examine whether non-human primates with different neocortical sizes show different abilities regarding working memory for action, the performance of squirrel monkeys (Saimiri sciureus) and common marmosets (Callithrix jacchus) in a kind of delayed-response task was compared. In this task, subjects were required to select a response based on short-term memory of the outcome of their own prior action, which requires working memory of action. These monkeys have a similar phylogenetic status (i.e. Ceboidea), but the size of the neocortex relative to the rest of the brain (relative size of the neocortex) is quite different. We found that both two species could attend to and remember their own actions and could select a response based on that memory. However, the performance level was higher for squirrel monkeys than for marmosets. These results suggest that non-human primates with differentially developed neocortices have different abilities regarding working memory of action.

Journal Article↗
PubMed2005

The role of the hippocampus in object recognition in rats: examination of the influence of task parameters and lesion size.

Studies examining the effects of hippocampal lesions on object recognition memory in rats have produced conflicting results. The present study investigated how methodological differences and lesion size may have contributed to these discrepancies. In Experiment 1 we compared rats with complete, partial (septal) and sham hippocampal lesions on a spontaneous object recognition task, using a protocol previously reported to result in deficits following large hippocampal lesions . Rats with complete and partial hippocampal lesions were unimpaired, suggesting the hippocampus is not required for object recognition memory. However, rats with partial lesions showed relatively poor performance raising the possibility that floor effects masked a deficit on this group. In Experiment 2, we used a second spontaneous object recognition protocol similar to that used by the two other studies that have reported deficits following hippocampal lesions . Rats with complete hippocampal lesions were significantly impaired, whereas rats with partial lesions were unimpaired. However, the complete lesion group showed less object exploration during the sample phase. Thus, the apparent recognition memory deficit in Experiment 2 may be attributable to differential encoding. Together, these findings suggest that the hippocampus is not required for intact spontaneous object recognition memory. These findings suggest that levels of object exploration during the sample phase may be a critical issue, and raise the possibility that previous reports of object recognition deficits may be due to differences in object exploration rather than deficits in object recognition per se.

Analysis of Variance↗
PubMed2001

Naming and verbal memory skills in adults with Attention Deficit Hyperactivity Disorder and Reading Disability.

Research suggests that children with Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) can be differentiated based on their performance on measures of naming and verbal memory. It is not known whether this same pattern characterizes adults with these disorders. In this study, adults with and without ADHD and RD were compared on naming and verbal memory abilities. Results did not support the hypothesis that adults with ADHD and RD are significantly different from each other, or from a contrast group, on naming and verbal memory measures after controlling for Full-Scale IQ (FSIQ). These results were replicated across two sets of classification criteria used to identify diagnostic groups. Factors that could account for the inconsistency in research findings with children and adult subjects are discussed.

Adolescent↗
PubMed2001

The association between antisaccade task and working memory task performance in schizophrenia and bipolar disorder.

To date, the research literature has yielded conflicting reports regarding the specificity of antisaccade deficits to schizophrenia. We sought to examine antisaccade and working memory task performance in schizophrenia patients and bipolar patients, as well as to examine the relationship between the two tasks in both patient populations. Thirty-four schizophrenia patients, 20 bipolar patients, and 30 nonpatient controls were administered saccadic inhibition (antisaccade), working memory, and sensorimotor tasks. Compared with the controls, the schizophrenia patients displayed both antisaccade deficits and working memory deficits. In contrast, the bipolar patients produced significantly more errors on the antisaccade task than the controls, though the bipolar group performed similarly to the control group on the working memory task. Mediational analyses demonstrated that working memory partially mediates the relationship between patients' diagnostic group status and antisaccade task performance; working memory performance contributed uniquely to the prediction of antisaccade task performance in the two patient groups. Antisaccade deficits do not appear specific to schizophrenia. The results suggest that in schizophrenia, working memory and antisaccade tasks are tapping similar cognitive processes, whereas in bipolar patients the processes underlying antisaccade and working memory performance are disparate.

Adult↗
PubMed2000

A role for MHC class II antigen processing in B cell development.

For mature B cells, the encounter with foreign antigen results in the selective expansion of the cells and their differentiation into antibody secreting cells or memory B cells. The response of mature B cells to antigen requires not only antigen binding to and signaling through the B cell antigen receptor (BCR) but also the processing and presentation of the BCR bound antigen to helper T cells. Thus, in mature B cells, the ability to process and present antigen to helper T cells plays a critical role in determining the outcome of antigen encounter. In immature B cells, the binding of antigen results in negative selection of the B cell, inducing apoptosis, anergy or receptor editing. Negative selection of immature B cells requires antigen induced signaling through the BCR, analogous to the signaling function of the BCR in mature B cells. However, the role of class II antigen processing and presentation in immature B cells is less well understood. Current evidence indicates that the ability to process and present antigen bound to the BCR is a late acquisition of developing B cells, suggesting that during negative selection B cells may not present BCR bound antigen and interact with helper T cells. However, the expression of class II molecules is an early acquisition of B cells and recent evidence indicates that the expression of class II molecules early in development is required for the generation of long lived mature B cells. Here we review our current understanding of the processing and presentation of antigen by mature B cells and the role for antigen processing and class II expression during B cell development.

Animals↗
PubMed2005

Establishment and maintenance of long-term murine gammaherpesvirus 68 latency in B cells in the absence of CD40.

Murine gammaherpesvirus 68 (gammaHV68), like Epstein-Barr virus (EBV), establishes a chronic infection in its host by gaining access to the memory B-cell reservoir, where it persists undetected by the host's immune system. EBV encodes a membrane protein, LMP1, that appears to function as a constitutively active CD40 receptor, and is hypothesized to play a central role in EBV-driven differentiation of infected naive B cells to a memory B-cell phenotype. However, it has recently been shown that there is a critical role for CD40-CD40L interaction in B-cell immortalization by EBV (K.-I. Imadome, M. Shirakata, N. Shimizu, S. Nonoyama, and Y. Yamanashi, Proc. Natl. Acad. Sci. USA 100:7836-7840, 2003), indicating that LMP1 does not adequately recapitulate all of the necessary functions of CD40. The role of CD40 receptor expression on B cells for the establishment and maintenance of gammaHV68 latency is unclear. Data previously obtained with a competition model, demonstrated that in the face of CD40-sufficient B cells, gammaHV68 latency in CD40-deficient B cells waned over time in chimeric mice (I.-J. Kim, E. Flano, D. L. Woodland, F. E. Lund, T. D. Randall, and M. A. Blackman, J. Immunol. 171:886-892, 2003). To further investigate the role of CD40 in gammaHV68 latency in vivo, we have characterized the infection of CD40 knockout (CD40(-/-)) mice. Here we report that, consistent with previous observations, gammaHV68 efficiently established a latent infection in B cells of CD40(-/-) mice. Notably, unlike the infection of normal C57BL/6 mice, significant ex vivo reactivation from splenocytes harvested from infected CD40(-/-) mice 42 days postinfection was observed. In addition, in contrast to gammaHV68 infection of C57BL/6 mice, the frequency of infected naive B cells remained fairly stable over a 3-month period postinfection. Furthermore, a slightly higher frequency of gammaHV68 infection was observed in immunoglobulin D (IgD)-negative B cells, which was stably maintained over a period of 3 months postinfection. The presence of virus in IgD-negative B cells indicates that gammaHV68 may either directly infect memory B cells present in CD40(-/-) mice or be capable of driving differentiation of naive CD40(-/-) B cells. A possible explanation for the apparent discrepancy between the failure of gammaHV68 latency to be maintained in CD40-deficient B cells in the presence of CD40-sufficient B cells and the stable maintenance of gammaHV68 B-cell latency in CD40(-/-) mice came from examining virus replication in the lungs of infected CD40(-/-) mice, where we observed significantly higher levels of virus replication at late times postinfection compared to those in infected C57BL/6 mice. Taken together, these findings are consistent with a model in which chronic virus infection of CD40(-/-) mice is maintained through virus reactivation in the lungs and reseeding of latency reservoirs.

Animals↗
PubMed2006

Use of Hachinski Ischemic Score in the memory clinic: Thai experience.

BACKGROUND: The validity ofHachinski Ischemic Score (HIS) in differentiating between Alzheimer's disease (AD) and Vascular dementia (VaD) has been questioned and compared with the gold standard autopsy. OBJECTIVE: To confirm that the HIS can be used to differentiate related VaD from AD in a Thai population. MATERIAL AND METHOD: A prospective study of 398 patients who were attending the Memory Clinic, at Siriraj Hospital between January 2001 and October 2003. RESULTS: The 214 patients, with a mean age of 71.15 + 10.20 years, were classified as AD, VaD or mixed dementia (AD with cerebrovascular disease) in proportion of 60.2%, 30.4%, and 9.3% respectively. The authors propose HIS at 5 as a cut off point to differentiate patients with AD and those with VaD or AD with cerebrovascular disease with sensitivity of 85.3% and specificity of 72.9%. CONCLUSION: The HIS can be applied to differentiate dementia related vascular etiology from AD in a Thai population.

Aged↗
PubMed1998

Parental autobiographical memory: is this a helpful clinical measure in behavioural child management?

OBJECTIVES: The major hypothesis was that specificity scores on the Parent-Child Autobiographical Memory Test (PCAMT; Hutchings, 1996) would differentiate between mothers of children referred to a child and adolescent mental health service for behavioural management, and those who were not referred. Within the referred sample, the objective was to examine the relationships between the PCAMT, mental health (Beck Depression Inventory; Beck, Ward, Mendelson, Mock & Erbaugh, 1961; General Health Questionnaire; Goldberg, 1972) and socio-economic deprivation (SED5; Hutchings, 1996) and measures of outcome (Eyberg Child Behavior Inventory; Eyberg, 1980). DESIGN: Pre-treatment measures on the PCAMT for the group of mothers whose children were referred were compared with measures on the PCAMT from a group of mothers of non-referred children of similar ages. Within the mothers of the referred sample, correlations of the PCAMT with other measures were examined, pre- and post-treatment. METHODS: Pre-treatment PCAMT scores from 26 mothers of children with behaviour management problems from consecutive referrals to a child and adolescent mental health service were compared with PCAMT scores from 22 mothers of children of a similar age from a local playgroup. Within the referred group, the PCAMT was administered before (N = 26) and after (N = 16) treatment. The 16 treated families received behavioural management advice. RESULTS: The PCAMT distinguished between parents of children referred for behavioural management advice and a non-clinical sample. Within the referred group it also distinguished between those who received treatment and those who did not attend treatment. CONCLUSIONS: The PCAMT is considered to have the potential of being a useful instrument for identifying referred children whose mothers may not attend for treatment and possibly for identifying those mothers who would benefit most from concentrating on attending and observation skills in child management training.

Adult↗
PubMed1991

Electrophysiological studies of the functions of the nucleus basalis in primates.

In summary, the studies reviewed here have indicated which neural functions might be directly influenced by the nucleus basalis. Basalis neurons do not appear to be directly involved in trial-specific memory because, in memory tasks, they have non-differential responses that do not correspond to the information being remembered by the monkey. Similarly, basalis neurons do not appear to be related to movements because, in a go/no-go task, similar neuronal responses occur whether the animal moves or does not move, and, in a delayed response task, different neuronal responses occur during the same arm movement made under different conditions. Basalis neurons also respond differently to the same sensory stimuli presented under different conditions, which indicates that the nucleus basalis is not involved in basic sensory perception. The responses of basalis neurons therefore appear to be strongly influenced by the context or behavioral significance of stimuli. Many basalis neurons respond to appetitive stimuli. In trained animals, the most frequently observed responses have been to a water reward or to stimuli that consistently precede the reward. In naive, thirsty animals, a large proportion of basalis neurons respond to the delivery of water. However, a large number of neurons also respond to an aversive air puff, which indicates that the nucleus basalis cannot be exclusively related to appetitive stimuli. Although some basalis neurons apparently respond only to the appetitive stimulus and others respond only to the aversive stimulus, the majority appear to respond similarly to both stimuli. In particular, almost all of the neurons whose response magnitudes covary with the volume of the water respond similarly to the air puff. Hence, the neurons that appear most likely to be related to the appetitive component of the water are also responsive to an aversive stimulus. Basalis neurons may therefore be related to some common characteristic of aversive and appetitive stimuli, such as the arousing quality of these stimuli. The hypothesis that most basalis neurons are particularly responsive to arousing stimuli could account for the abundance of responses to rewards and stimuli associated with rewards. These phasic responses of basalis neurons are hypothesized to be related to a transient increase in the cortical activation component of arousal, just as the tonic activity of basalis neurons appears to be related to sustained cortical activation.

Animals↗
PubMed2005

Encoding a motor memory in the older adult by action observation.

The ability of motor training to encode a motor memory is reduced in older adults. Here, we tested the hypothesis that training-dependent memory encoding, an issue of relevance in neurorehabilitation, is enhanced in elder individuals by action observation which alone can contribute to learning processes. A group of 11 healthy older adults participated in this study, which consisted of three randomized counterbalanced sessions on different days testing the effects of motor training (MT) alone, action observation (AO) alone, and a combination of both (MT + AO) on motor memory encoding. The combination of MT + AO formed a motor memory in the primary motor cortex and differentially modulated motor cortical excitability in muscles that were agonist and antagonist with respect to the training task, but MT or AO alone did not. These results suggest that action observation can enhance the effects of motor training on memory encoding protocols in the older adult, possibly through Hebbian modulation of intracortical excitatory mechanisms.

Aged↗