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PubMed1995

Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers.

Costimulatory interactions between T and B lymphocytes are crucial for T cell activation and B cell proliferation and differentiation. We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags. Germinal center (GC) formation in response to a Td Ag was inhibited completely by the early administration of anti-CD40L or anti-B7-2 Abs. Later in the response, established GCs remained sensitive to anti-CD40L but were resistant to treatment with anti-B7-2. However, Ig hypermutation was reduced dramatically in GCs of anti-B7-2-treated mice and humoral memory was impaired. Early administration of anti-CD40L reduced serum Ab levels to approximately 10% of controls, whereas early treatment with anti-B7-2 reduced Ab production by only 50%. Later treatments with either Ab had no effect on Ab production. Response to a type II Ti Ag was more resistant than Td responses to interruption of costimulatory interactions. Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment. Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.

Animals↗
PubMed1976

Memory changes after unilateral electroconvulsive therapy with different electrode positions.

In the course of a series into the effects of unilateral electroconvulsive therapy on memory functions,double-blind cross-over intraindividual comparison were performed after the second and third treatment in patients suffering from depressive syndrome. The main aim of the project, which is still in course, was to explore the possibility of a further reduction of the side-effects of this antidepressant method. Three separate comparisons were performed between unilateral nondominant temporo-parietal ECT and (a) unilateral dominant temporo-parietal ECT, (b) unilateral non-dominant fronto-parietal ECT, (c) unilateral non-dominant fronto-fronto ECT (Figure 1). The treatments were given under total anaesthesia and with subtotal muscle relaxation. Four memory tests were administered three hours after the second and the third ECT, the treatment methods being allocated at random. The 30 Word-Pair Test is mixed audio-visual recall verbal test. The 30 Figure Test is mainly visual recognition test with items which can be easily verbally patterned. Further, two visual recognition tests, the 30 Face Test and the 30 Geometrical Figure Test, composed of not easily verbalized items were administered. For each test, three memory scores were obtained, immediate memory score (IMS, immediately after the presentation of the items, three hours after ECT), delayed memory score (DMS, three hours after IMS) and their differenc, forgetting score (FS). IMS is considered to be a function of the hypothetical memory variable, learning, and FS a function of the variable retention. DMS is related to both learning and retention. When non-dominant and dominant temporo-parietal ECT are compared, there are, after non-dominant ECT, significantly lower IMS and DMS in the 30 Face Test but only lower IMS in the 30 Geometrical Figure Test. The difference in DMS for the 30 Word-Pair Test is in the opposite direction (Figure 2). In the comparison between non-dominant temporo-parietal vs non-dominant fronto-frontal ECT, a slightly, non-significant, lower IMS in the 30 Face Test is apparent (Figure 4). Other important trends are not found in any of the studies (Figures 2-4). The results show that differential effects are obtained with different memory material when dominant and non-dominant electrode positions are used in unilateral ECT. The results are discussed in relation to the question whether high level perceptive function or memory is involved in the encoding-storage of complex non-verbal material in the non-dominant hemisphere.

Adult↗
PubMed1999

The effect of caffeine in animal models of learning and memory.

In the present investigation we studied the effect of caffeine on memory task inhibitory avoidance and habituation to a new environment. Caffeine impaired retention scores in mice submitted to inhibitory avoidance and habituation when administered 30 min before training at the doses of 10-30 mg/kg. These effects cannot be explained by state-dependency since the administration of caffeine 30 min before the test session did not reverse the effect of pre-training caffeine administration, but can more probably be explained by an impairment in the acquisition or by interference with attentional processes. On the other hand, caffeine improved the inhibitory avoidance (but not habituation) retention scores when administered immediately after the training or 30 min before the test session at the doses of 1-30 mg/kg or 3-10 mg/kg, respectively. These results suggest that caffeine differentially affects the different stages of memory processing and that this effect depends on particularities of the memory task under study.

Analysis of Variance↗
PubMed2002

Temporal determinants of long-term retention of olfactory memory in the cricket Gryllus bimaculatus.

Temporal determinants of olfactory long-term memory retention in the cricket Gryllus bimaculatus were studied. Elementary appetitive and aversive conditioning procedures, as well as a differential conditioning procedure, were applied. In appetitive conditioning, peppermint odour was paired with a water reward. In aversive conditioning, vanilla odour was paired with saline solution. In differential conditioning, an appetitive conditioning trial was followed by an aversive conditioning trial. The odour preference of crickets was tested before and 2 h, 1 day and 4 days after training by allowing the crickets to choose between peppermint or vanilla sources. Differential conditioning or appetitive conditioning alone led to long-lasting memory retention with no significant decay from 2 h to 4 days after training, but retention after aversive conditioning was absent 1 day after training. Studies using differential conditioning have shown (i) that four trials are sufficient to cause a saturated level of acquisition, (ii) that conditioning is successful when the conditioned stimulus is presented immediately or 5 s before the onset of presentation of the unconditioned stimulus, (iii) that the optimal interval between trials is 2-5 min, and (iv) that anaesthetic treatment with CO2 given immediately after training results in memory disruption but that anaesthetic-resistant memory develops fully 20 min after training. This study demonstrates that a differential conditioning procedure is particularly effective for the formation of long-term memory.

Animals↗
PubMed2005

[A case of primary progressive multiple sclerosis with onset of memory impairment].

We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS) presenting with chronic progressive memory impairment. From a couple of years prior to admission, she had developed impairment of her short-term memory. For example, she forgot her nephew's name, and spoke the same phrases again and again. She also sometimes forgot to turn off her gas stove and forgot things she bought in shops. Moreover, her mental activity gradually decreased and she became apathetic. However, she did not note her memory impairment, and had no hallucinations. She was admitted to our hospital on 20 May, 2003 because donepezil had been ineffective for treating her memory impairment. Neurologically, she showed bilateral horizontal gaze nystagmus, mild limb ataxia on the left and mildly ataxic gait. Neuropsychological examinations showed mildly impaired cognitive function, e.g., MMSE 25/30, WAIS-R full IQ 69 and especially in verbal short memory, which may represent temporal lobe dysfunction. Moreover, Benton's visual memory test revealed marked visual short-term memory impairment, while impaired performance on a Kana picking up test suggested mild to moderate attention impairment, which could have represented frontal lobe dysfunction. Brain MRI showed multiple T2-high plaque lesions close to the bilateral lateral ventricles, and bilateral optic nerve lesions enhanced by gadolinium. Also, spinal cord MRI showed a gadolinium enhanced lesion at Th5 on the left. Cerebral spinal fluid (CSF) examination showed normal cell count and protein level, and undetectable oligoclonal bands (OCB), but an elevated IgG index (1.1, normal < 0.85). Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally, indicating subclinical optic nerve lesions. She was thus diagnosed as having PPMS according to McDonald's diagnostic criteria for MS. 99mTc Single photon emission computed tomography (SPECT) showed a decreased cerebral blood flow (CBF) in the bilateral frontal and temporal lobes, which was consistent with her clinical features. PPMS patients generally present with chronic progressive spastic paraparesis and/or cerebellar ataxia. Cognitive impairments observed in PPMS are generally thought to be due to white matter lesions, i.e., subcortical dementia. However, some recent reports have shown MS patients with short-term memory impairment (antegrade amnesia) similar to cortical dementias such as Alzheimer's disease (AD). In such MS cases, visual short-term memory impairment seems characteristic of their cognitive impairment compared to AD cases. As well, the present case showed visual memory impairment as evaluated by Benton's memory test. Parietal and frontal lobes are reported to be important for verbal and visual working memory, respectively. Thus, in the present case, decreased CBF in the frontal and temporal lobes, which could have been due to a disconnection between cortices and subcortices caused by the white matter lesions, is consistent with the type of her cognitive dysfunction, i.e., notable visual memory impairment. PPMS may thus be an important disease as a differential diagnosis for chronic progressive dementia. Further neuropsychological and functional imaging studies will be necessary to achieve a better understanding of the mechanisms of cognitive impairment in PPMS.

Brain↗
PubMed1978

Acute confabulatory psychosis: a rare form of unipolar mania?

Emil Kraepelin's paper on false memories (Erinnerungsfälschungen) was probably the most extensive and incisive analysis of these phenomena ever made. Using his views as a starting point, the concept of confabulation is then defined in a Kraepelin-oriented manner, making it also applicable to the phantastic false memories found in some rarer forms of functional psychotic illness. Kraepelin and Leonhard have been preeminent in their concern with such clinical states; thus, Leonhard's confabulatory euphoria and confabulatory paraphrenia can be symptomatically and syndromally linked up with points of view on paranoid mania and confabulatory paraphrenia held by Kraepelin. An "ideally typical" case is also presented to highlight some of the difficulties involved in trying to distinguish mania from schizophrenia when the clinical picture is dominated by phantastic "functional" confabulations.

Adolescent↗
PubMed1999

The choose-short effect and trace models of timing.

The tuned-trace multiple-time-scale (MTS) theory of timing can account both for the puzzling choose-short effect in time-discrimination experiments and for the complementary choose-long effect. But it cannot easily explain why the choose-short effect seems to disappear when the intertrial and recall intervals are signaled by different stimuli. Do differential stimuli actually abolish the effect, or merely improve memory? If the latter, there are ways in which an expanded MTS theory might explain differential-context effects in terms of reduced interference. If the former, there are observational and experimental ways to determine whether differential context favors prospective encoding or some other nontemporal discrimination.

Animals↗
PubMed2002

Biological implications of genes differentially expressed in human hippocampus and spinal cord.

The hippocampus is involved in learning and memory of intellectual functions whereas the spinal cord carries sensory impulses from the trunk and limbs to the brain and it returns commands from the brain to the muscles and glands. The relative expression levels of genes in human hippocampus and spinal cord were determined using high-density cDNA-arrays. Validations by semi-quantitative RT-PCR, Northern, and Western analyses show good agreement with cDNA-array results. Those genes differentially expressed in hippocampus encode proteins that are involved either in the neuronal plasticity or learning and memory signaling cascades. Interestingly, those differentially expressed in the spinal cord encode proteins that are associated with the responses to spinal cord injuries. These results also demonstrate the feasibility of comparing a vast number of gene expression profiles between various brain regions for potential targets with respect to abnormal brain functions.

Adolescent↗
PubMed1987

Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation.

The Pgp-1 glycoprotein was identified on a minor (27%) subset of peripheral Lyt-2+ or L3T4+ T cells. In contrast, mature medullary-type thymocytes (Lyt-2+ L3T4-, Lyt-2- L3T4+) were nearly devoid of cells expressing detectable surface Pgp-1. The appearance of peripheral Pgp-1- T cells was found to be thymus dependent, as demonstrated by the diminished proportion of Pgp-1- T cells after thymectomy and their virtual absence in athymic nude mice. The subsequent acquisition of surface Pgp-1 was found to be a stable differentiation event occurring concomitantly with primary antigenic stimulation; selected Pgp-1- mature T cells from thymus or periphery acquired constitutive expression of Pgp-1 after stimulation in vitro with alloantigen or mitogens. These observations were extended by studies in vivo showing that immunization with various antigens augmented the percentage of Pgp-1+ spleen cells within the Lyt-2+ subset. Furthermore, the frequencies of antigen-specific CTLp, after immunization by any of three different antigens tested, were greatly enriched in the Pgp-1+ compared with the Pgp-1- subpopulations. Peritoneal exudate Lyt-2+ cells, after a localized allograft rejection, demonstrated a particularly prominent Pgp-1+ subpopulation (78%) that contained virtually all the allospecific cytolytic activity. A model consistent with all of these data proposes that mature thymocytes lacking surface Pgp-1 upon emigration to the periphery acquire its expression at the time of primary antigenic stimulation. Hence, expression of Pgp-1 among peripheral T cells is an important differentiation marker for identifying antigen-stimulated memory T cells.

Animals↗
PubMed2003

Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation.

In the present work, we demonstrate that interleukin (IL)-4 is able to rescue B cells from Trypanosoma cruzi-infected mice, counteracting the strong apoptotic signals that these cells received in vivo. We have observed that IL-4 restrains the apoptosis of immunoglobulin (Ig)M(+) and IgG(+) B cells from infected and normal mice without inducing them to proliferate. In addition, IL-4 does not modify the quantity or quality of the antibodies secreted by B cells from infected mice, as it blocks their terminal differentiation to plasma cells and favors memory pathway. It is interesting that the protective effect of IL-4 over B cells from infected mice is mediated, at least partly, by the down-regulation of Fas ligand (FasL) expression, which leads to interference in the apoptosis executed by these B cells through the Fas/FasL death pathway. Accordingly, a marked up-regulation of the "FasL gene repressor" class II transactivator was observed, suggesting that this would be one mechanism underlying the IL-4-mediated FasL down-regulation.

Animals↗
PubMed1996

Event-related potentials as indirect measures of recognition memory.

Event-related potentials (ERPs) were recorded during an auditory word-recognition task to determine whether they can be used as indirect measures of recognition memory, defined as the ability to differentiate learned from unlearned material when no overt recognition response from the subject is required. A modified version of the two-choice reaction time task developed by Allen, Iacono and Danielson (Allen et al., 1992) was used. In three recognition tasks, administered on two consecutive days, subjects were instructed to indicate recognition of recently learned words. These words were presented along with unlearned words and along with previously learned words which both required a non-recognition response. Recently learned target words as well as previously learned nontarget words elicited a centro-parietal positivity around 500-1000 ms post-stimulus. The size and onset of this late positivity (P300) were affected by the requirement of an overt recognition response. The results suggest that ERPs are sensitive to differences between learned and unlearned words, to some extent independently of the behavioral response. ERPs may therefore be used as indirect measures of recognition memory. In addition, because the present results held for stimuli presented in the auditory modality and because recognition indices were still observed after a one-day interval between learning and testing, this procedure might prove useful in various applications when the integrity of memory is in question.

Adolescent↗
PubMed1996

B cell differentiation and isotype switching is related to division cycle number.

The mature, resting immunoglobulin (Ig) M, IgD+ B lymphocyte can be induced by T cells to proliferate, switch isotype, and differentiate into Ig-secreting or memory cells. Furthermore, B cell activation results in the de novo expression or loss of a number of cell surface molecules that function in cell recirculation or further interaction with T cells. Here, a novel fluorescent technique reveals that T-dependent B cell activation induces cell surface changes that correlate with division cycle number. Furthermore, striking stepwise changes are often centered on a single round of cell division. Particularly marked was the consistent increase in IgG1+ B cells after the second division cycle, from an initial level of < 3% IgG1+ to a plateau of approximately 40% after six cell divisions. The relationship between the percentage of IgG1+ B cells and division number was independent of time after stimulation, indicating a requirement for cell division in isotype switching. IgD expression became negative after four divisions, and a number of changes centered on the sixth division, including the loss of IgM, CD23, and B220. The techniques used here should prove useful for tracking other differentiation pathways and for future analysis of the molecular events associated with stepwise differentiation at the single cell level.

Animals↗
PubMed1998

Cognitive loss in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

Aged↗
PubMed1990

Selective deficits in Alzheimer and parkinsonian dementia: visuospatial function.

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.

Adult↗
PubMed1999

Functional differences between memory and naive CD8 T cells.

To determine how murine memory and naive T cells differ, we generated large numbers of long-lived memory CD8(+) T cells and compared them to naive cells expressing the same antigen-specific receptor (T cell receptor; TCR). Although both populations expressed similar levels of TCR and CD8, on antigen stimulation in vitro memory T cells down-regulated their TCR faster and more extensively and secreted IFN-gamma and IL-2 faster than naive T cells. Memory cells were also larger, and when freshly isolated from mice they contained perforin and killed target cells without having to be restimulated. They further differed from naive cells in requiring IL-15 for proliferation and in having a greater tendency to undergo apoptosis in vitro. On antigen stimulation in vivo, however, they proliferated more rapidly than naive cells. These findings suggest that, unlike naive T cells, CD8 memory T cells are intrinsically programmed to rapidly express their effector functions in vivo without having to undergo clonal expansion and differentiation.

Animals↗
PubMed1997

Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection.

Mice sensitized to the G (attachment) or F (fusion) glycoproteins of respiratory syncytial virus (RSV) expressed different patterns of cytokine production and lung pathology when challenged by intranasal infection with RSV. Five days after challenge, mice sensitized to G glycoprotein produced high levels of interleukin-4 (IL-4) and IL-5 in the lungs and spleens and developed extensive pulmonary eosinophilia, while mice sensitized to F glycoprotein produced IL-2 and developed a mononuclear cell infiltration. Memory lymphocytes isolated 2 weeks after intranasal challenge of mice primed to the G or F glycoprotein secreted only IL-2 and gamma interferon (IFN-gamma) when stimulated with RSV. IL-4 and IL-5 production characteristic of Th2-type effectors in the lung was observed only after multiple rounds of in vitro stimulation of RSV G-specific memory T lymphocytes with antigen. Also IFN-gamma production appeared to play only a minor role in the expression of pulmonary pathology characteristic of Th1 or Th2 T-lymphocyte responses, because mice genetically deficient in IFN-gamma production by gene disruption displayed the same pattern of pulmonary inflammation to RSV infection after priming to RSV F or G as conventional mice. These results suggest that effector T lymphocytes exhibit a different pattern of cytokine production than memory T-lymphocyte precursors precommitted to a Th1 or Th2 pattern of differentiation. Furthermore, these observations raise the possibility that the cytokine response of human memory T lymphocytes after a single exposure to antigen in vitro may not accurately reflect the cytokine response of differentiated effector T lymphocytes at the site of infection in vivo.

Animals↗
PubMed2000

[Reversible memory disorders in an older patient caused by epilepsy].

Memory impairment in a 63-year-old man was the most prominent expression of partial epileptic seizures from the temporal lobe, probably resulting from a head injury. Treatment with antiepileptic drugs resulted in complete recovery. This case illustrates that epilepsy should be considered in the differential diagnosis in elderly patients with an isolated memory disorder. The diagnosis is made by clinical methods and may be confirmed by electroencephalography.

Anticonvulsants↗
PubMed2006

Phenotypic and functional status of intrahepatic T cells in chronic hepatitis C.

Polychromatic flow-cytometric assays were used to analyze paired intrahepatic and peripheral lymphocyte samples from 37 patients with chronic hepatitis C. Compared with peripheral cells, intrahepatic T cells were selectively enriched with CD45RO+ memory T cells but had a lower percentage of CD4+ T cells expressing the differentiation markers CD27 and CD28. The percentage of intrahepatic CD45RO+ and CD28+ T cells correlated with the degree of liver inflammation, which suggests that memory T cells at relatively early stages of differentiation are directly involved in liver inflammation. Despite their memory phenotype, intrahepatic T cells were defective in proliferation capability, produced less interferon- gamma in response to stimulation by T cell receptor, and contained less perforin but expressed higher levels of Fas and Fas ligand, compared with their counterparts in peripheral blood. The distinct characteristics of intrahepatic T cells suggest that they play an important role in the immunopathogenesis of chronic hepatitis C.

Adult↗