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PubMed2001

Explicit and implicit memory biases in depression and panic disorder.

The purpose of the present study was to investigate the presence of a bias for emotional information (panic-related, depression-related, positive and neutral) in explicit memory and implicit memory (by means of free recall and word-stem completion tasks, respectively) among depressed (N=20) and panic (N=20) patients. Three different encoding conditions (graphemic, semantic and self-reference) were used. The results of this study failed to show the existence of a mood-congruent memory bias for both implicit and explicit memory in these emotional disorders. According to the correlational analyses performed, differences among categories of emotional words meant less than the difference among various types of encoding and memory bias in order to differentiate among groups.

Adult↗
PubMed2002

Vaccinology for control of apicomplexan parasites: a simplified language of immune programming and its use in vaccine design.

Most mammalian immune systems and parasites have co-evolved over the millennia, interacting within a common environment and communicating through a common language. This language is comprised of copious dialects in which a variety of host innate and acquired immune pathways actively interact with a multitude of parasite-specific survival strategies. Nonetheless, a simplified language is likely present since the same basic molecular and cellular mechanisms are associated with resistance or susceptibility to parasite infection. Protective immunity against protozoa within the phylum Apicomplexa (e.g. Cryptosporidia, Eimeria, Neospora, Plasmodia and Toxoplasma) is generally CD4+ T cell-dependent and elicited along the IL-12/IFN-gamma/iNOS effector axis. This simplified language can be decoded in part by significant advances in understanding naïve T cell activation, differentiation and generation of immunologic memory. Vaccine adjuvants and new immunisation strategies for generation of more potent immunity can also be viewed through this common language lens. The aim of this paper is to summarise recently published fundamental immunology studies, their relevance through examples in specific coccidian-host immune dialects, and how this simplified language can be used for the more rationale design of parasite vaccine control strategies.

Adjuvants, Immunologic↗
PubMed1983

Radial arm maze performance of mice: acquisition and atropine effects.

CD-1 mice were successfully trained in a six-arm radial maze in which half of the arms were baited, a procedure which had been used to differentiate between reference and working memory. Stable performance was achieved following eight daily training sessions, as measured by decreasing running time and number of errors. This finding strengthens the foraging hypothesis as a basis for the performance of rodents in the radial maze. Acute subcutaneous administration of the cholinergic antagonist atropine sulfate (1-6 mg/kg) to trained mice produced dose-related increases in running time and working memory errors, with a slight decrease in reference memory errors. This is in agreement with other studies on the role of the cholinergic system in memory processes. The peripheral cholinergic blocker, atropine methyl nitrate (4 mg/kg), somewhat increased running time without decreasing performance accuracy. In contrast to the prolonged pharmacological and physiological effects of atropine, behavioral decrements disappeared within 3 hr. It is concluded that mice trained in the radial arm maze may be used for screening of the effects of drugs on cognitive function.

Animals↗
PubMed1998

ARTMAP-IC and medical diagnosis: Instance counting and inconsistent cases.

For complex database prediction problems such as medical diagnosis, the ARTMAP-IC neural network adds distributed prediction and category instance counting to the basic fuzzy ARTMAP system. For the ARTMAP match tracking algorithm, which controls search following a predictive error, a new version facilitates prediction with sparse or inconsistent data. Compared to the original match tracking algorithm (MT+), the new algorithm (MT-) better approximates the real-time network differential equations and further compresses memory without loss of performance. Simulations examine predictive accuracy on four medical databases: Pima Indian diabetes, breast cancer, heart disease, and gall bladder removal. ARTMAP-IC results are equal to or better than those of logistic regression, K nearest neighbour (KNN), the ADAP preceptron, multisurface pattern separation, CLASSIT, instance-based (IBL), and C4. ARTMAP dynamics are fast, stable, and scalable. A voting strategy improves prediction by training the system several times on different orderings of an input set. Voting, instance counting, and distributed representations combine to form confidence estimates for competing predictions.

Journal Article↗
PubMed1996

Cytotoxic T lymphocyte responses to Epstein-Barr virus.

Epstein-Barr virus induces a potent cytotoxic T lymphocyte response in man that is preferentially directed towards a particular subset of the virus latent cycle antigens; the immunodominance of these proteins, apparent in both primary and memory responses, may reflect some differential access to the HLA class I processing pathway. Effector cells recognizing these immunodominant antigens can reverse the growth of virus-induced lymphoproliferative lesions in immunosuppressed patients; however, responses to some of the subdominant latent proteins will be needed to target other virus-positive tumours.

Herpesvirus 4, Human↗
PubMed1997

Sequential and coordinative complexity in time-accuracy functions for mental arithmetic.

Time-accuracy functions for tasks involving single-digit mental addition and subtraction were derived in a sample of 18 younger (mean age = 21.7 years) and 16 older adults (mean age = 68.8 years). Sequential complexity was manipulated by varying the number of operations (5 vs. 10); coordinative complexity was induced by bracketing. Age differences were apparent in the coordinative conditions, even though no age difference was present in the sequential conditions. This indicates that the age difference under conditions of high coordinative demands could not be attributed solely to a decline in basic speed of processing. The Age x Complexity interaction was due to larger onset times and lower asymptotic performance by the older adults in the coordinative conditions but not due to to rate of approach to the asymptote. This implies that coordinative demands do not differentially hurt access from semantic memory in older adults; however, coordinative demands do have disproportionately negative consequences for computation speed and self-monitoring in older adults.

Adult↗
PubMed2003

Chemokines in lymphocyte trafficking and intestinal immunity.

Lymphocyte migration through gut-associated lymphoid tissues (GALT) and into intestinal effector sites is critical to intestinal immune system function and homeostasis. Chemokines contribute to lymphocyte trafficking by triggering integrin activation and firm arrest in the vasculature and mediating chemotactic localization within tissues. Several chemokines have been identified that are expressed in the GALT and/or the intestines themselves (TECK/CCL25, MEC/CCL28, and MIP-3alpha/CCL20) and play a role in intestinal lymphocyte localization, including unification of intestinal and other mucosa-associated effector sites; segmental specialization of the intestines; and subset selective localization to the intestines. This review examines the role of these chemokines (and their receptors CCR9, CCR10, and CCR6, respectively) in lymphocyte homing to the GALT, in the induction and differentiation of intestinal effector and memory lymphocytes, and in the homeostatic and inflammatory localization of lymphocytes to the intestines.

Animals↗
PubMed2002

Dendritic cells, chemokine receptors and autoimmune inflammatory diseases.

Dendritic cells (DC) have been implicated in the induction of autoimmune diseases and have been identified in lesions associated with several autoimmune inflammatory diseases. Since DC are regarded as the professional antigen-presenting cell (APC) of the immune system and the only APC capable of activating naïve T cells, they are likely to play a significant role in breaking tolerance of self-reactive lymphocytes and in supporting autoimmune responses in these diseases. A number of studies have revealed that small molecular weight chemotactic proteins known as chemokines are present within the autoimmune lesions and may contribute to the recruitment not only of DC populations, but also of immune cells such as T cells, B cells, neutrophils and monocytes into the site, and to the formation of organized lymphoid tissue structures within the target organ. The focus of this review will be a discussion of the role of chemokines in the recruitment of DC in human autoimmune inflammatory disorders, specifically the trafficking of DC into the inflammatory sites and the subsequent migration of differentiated DC from the inflammatory sites into the draining lymph nodes. Once DC are properly positioned within the lymph nodes, circulating antigen specific naïve T cells can interact with DC and become activated, clonally expanded and stimulated to undergo differentiation into antigen-experienced memory T cells. Subsequent reactivation of memory T cells that enter the autoimmune lesions by DC present in the inflammatory lesion is thought to play a central role in tissue inflammation.

Adult↗
PubMed2004

Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells.

Autoimmune disease results from the dysregulation of basic tolerogenic processes designed to control self/non-self-discrimination. Approaches to treat autoimmunity have focused historically on potent immunosuppressives that block the activation and expansion of antigen-specific T cells before they differentiate into pathogenic T cell responses. These therapies are very efficient in reducing clonal expansion and altering early signaling pathways. However, once the pathogenic responses are established (i.e., autoimmunity), the interventions are less effective on activated and differentiated T cell subsets (including memory T cells) or acting in the presence of an inflammatory milieu to abort immune responses at the target tissue and systemically. Moreover, the current immunotherapies require continuous use because they do not redirect the immune system to a state of tolerance. The continuous treatment leads to long-term toxicities and can profoundly suppress protective immune responses targeted at viruses, bacteria, and other pathogens. Over the past decade, there have been tremendous advances in our understanding of the basic processes that control immune tolerance. Among the most exciting has been the identification of a professional regulatory T cell subset that has shown enormous potential in suppressing pathologic immune responses in autoimmune diseases, transplantation, and graft vs. host disease. In this review, we summarize current efforts to induce and maintain tolerance in the autoimmune diabetes setting by using therapeutic vaccination with CD4(+)CD25(+) regulatory T cells. Emphasis will be placed on approaches to exploit regulatory T cells either directly or through the use of anti-CD3 immunotherapy.

Animals↗
PubMed2004

Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection.

Features of the lymphocyte population in systemic lupus erythematosus (SLE) include a disordered B cell profile and production of autoantibodies. An additional distinctive perturbation is the overexpression of V4-34-encoded serum immunoglobulins (Ig). A similar rise in V4-34-encoded Ig occurs in normal subjects following infection with certain herpesviruses, and is found in Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). To assess common and distinctive features of B cells in patients with SLE and IM, we compared the B cell profile and V4-34 gene involvement in patients with SLE and IM. B cell profiles from patients with IM paralleled those of patients with SLE, showing a differential loss of naïve and memory B cells and the maintenance of plasmablast/early plasma cells. Class-switched V4-34-encoded IgG from plasmablast/early plasma cells was evident both in patients with SLE and IM and revealed common features of oligoclonal expansions with most having undergone somatic hypermutation. It has been proposed that, in healthy individuals, expression of the V4-34 gene is specifically censored prior to isotype switch as a control on autoreactivity. If so, censoring is bypassed following EBV infection, after which equilibrium is restored. Continuing high serum levels in SLE may arise either by disordered regulation, or by subclinical reactivation of endogenous virus.

Amino Acid Sequence↗
PubMed2006

Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection.

We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVDeltanef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVDeltanef animals were predominantly CD27-CD28-CD45RAlowCCR7-CCR5-, consistent with an effector-memory subset, and included a fully differentiated CD45RA+CCR7- subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA-CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7-CD4+ subset from SIVDeltanef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIVDeltanef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.

Animals↗
PubMed2006

Cellular immune responses to diluted and undiluted aventis pasteur smallpox vaccine.

BACKGROUND: Recent primary vaccine trials of diluted Aventis Pasteur smallpox vaccine (APSV) demonstrated that immunization "take" rates, defined by the presence of a vesicle or pustule ("take") at the inoculation site 6-11 days after immunization, did not differ between the dilution groups. To our knowledge, there have been no studies that examine the cellular immune response or that distinguish CD4(+) T cell responses from CD8(+) T cell responses after primary immunization with varying dilutions of APSV. METHODS: In the present study, we examined the cellular immune response in vaccinia-naive healthy adults (n=91) receiving inoculations with an undiluted or diluted (1:5 and 1:10) suspension of the APSV, using an intracellular cytokine staining assay. RESULTS: The diluted vaccine induced vaccinia virus (VV)-specific CD4(+) and CD8(+) T cell responses 1 month after primary immunization that were comparable to those induced by undiluted vaccine. The cellular immune responses were correlated with the reactogenicity profile of subjects and did not differ between dilution groups. Furthermore, expression of the interleukin-7 receptor alpha chain, which has been proposed to distinguish antigen-specific T cells that differentiate into long-lived memory T cells, did not differ among groups, suggesting that dilution of the vaccine does not affect the quantity of VV-specific memory T cells. CONCLUSIONS: APSV is an effective smallpox vaccine inducing strong humoral and cellular immune responses after a primary immunization even at diluted doses.

CD4-Positive T-Lymphocytes↗
PubMed1996

Use of image enhancement during lithotripsy.

Renal excursion during breathing is inevitable and is a cause of poor localization during extracorporeal shock-wave lithotripsy (SWL), which in theory might lead to poor treatment results. Eighty-one patients underwent lithotripsy treatment with and without the use of an image enhancement system designed for use with the Dornier MPL9000 lithotripter. This device contains a memory incorporated into a separate differential grayscale monitor, which allows the stone image to be stored. Shockwave release is enabled only when this image corresponds to the real-time image on the lithotripter ultrasound monitor. No improvement in success rates was found using this system, although upper-pole stones appeared to be fragmented more successfully. Overall, the results were favorable in both groups after a single treatment. Further work is needed to establish whether image enhancement is capable of improving the success rates and reducing the side effects of lithotripsy by better targeting.

Adult↗
PubMed2003

Effect of zinc supplementation of pregnant women on the mental and psychomotor development of their children at 5 y of age.

BACKGROUND: A negative effect of prenatal zinc deficiency on brain function has been well established in experimental animals, but this association in humans is controversial. OBJECTIVE: We evaluated the effect of prenatal zinc supplementation on the mental and psychomotor development of 355 children whose mothers participated in a double-blind trial of zinc supplementation that resulted in increased head circumference and birth weight. DESIGN: The children took 6 tests-the Differential Ability Scales, Visual Sequential Memory, Auditory Sequential Memory, Knox Cube, Gross Motor Scale, and Grooved Pegboard tests-at a mean age of 5.3 y. The scores were compared between the children of women who received a daily oral dose of 25 mg Zn during the second half of pregnancy and the children of women who received placebo. RESULTS: There were no differences in the test scores of neurologic development between the 2 groups. We analyzed the scores in 4 subgroups on the basis of maternal body mass index, because the increases in birth weight and head circumference due to the supplementation occurred only in the children of women with a body mass index (in kg/m(2)) < 26.0 in the original trial. No differences in the scores were found between these subgroups. CONCLUSIONS: Zinc supplementation of women in the latter half of pregnancy had no effect on the neurologic development of their children at age 5 y. It is not known whether our findings of no positive effect in the population with apparently inadequate zinc nutriture can be readily extrapolated to other populations.

Adult↗
PubMedDate not supplied

Familial primary progressive aphasia.

Primary progressive aphasia (PPA) is a neurodegenerative disease presenting with isolated, progressive, language dysfunction. After at least 2 years, dementia may develop, but the aphasia predominates. Few families with hereditary PPA have been reported; some have autosomal dominance. A chromosome 17 mutation in tau exon 13 has been found in one family, and a few have linkage to chromosome 17. However, early appearance of prominent memory, behavior, and motor impairments differentiates these patients from typical PPA. The objective was to report clinical features, pathology, and genetic analysis of a family with typical PPA. We report three siblings with the typical clinical syndrome of PPA. Each presented with word-finding difficulties and early anomia. Ages at onset were 60, 61, and 65 years. Aphasia was the only symptom for at least 2 years. A nonaffected brother is 75 years of age. Family history review found no other affected relatives. Neuropathology in one patient demonstrated "dementia lacking distinctive histopathology" with ubiquitin-positive cortical neurons. DNA analysis of the proband did not detect any known mutation in tau exons 1-5, 7, or 9-13. To our knowledge, this is the first family presenting with hereditary aphasia in which typical PPA occurs in all affected members.

Age of Onset↗
PubMed2005

Immunological strategies targeting B cells in organ grafting.

After delayed-type hypersensitivity and T cell cytotoxicity, the production of alloantibodies is the third effector mechanism contributing to graft injury. Histological characterization of antibody-mediated rejection and the detection of donor-reactive antibodies have highlighted the role of humoral immunity in acute and chronic rejection. A potential way of achieving central B cell tolerance is to induce complete chimerism with a myeloablative regimen and bone marrow transplant. However, nonmyeloablative regimens have been developed to create a state of "mixed chimerism" in patients without hematologic malignancies. Other strategies targeting B cells have been developed for the management of "high risk" clinical situations, including highly sensitized patients and transplantation with a positive crossmatch. These strategies have been extended to ABO incompatible transplantations and xenotransplantations. We will review therapeutic regimens that allow the removal or neutralization of pathogenic antibodies (immunoadsorption, plasmapheresis, intravenous globulins) and the blockade of memory B cell proliferation and differentiation into plasmocytes, including cyclophosphamide, the tacrolimus/mycophenolate mofetil combination, and anti-CD20 antibodies.

Acute Disease↗
PubMed2006

B-cell activity of polyclonal antithymocyte globulins.

Polyclonal antithymocyte globulins (AThG) are a subset of antilymphocyte antibody preparations derived from the sera of rabbits or horses immunized with unfractionated cells isolated from pediatric human thymi. In vivo, AThG preparations have been used to successfully treat antibody mediated rejection in kidney transplant recipients. In vitro, AThG can induce apoptosis of naïve and memory B cells and terminally differentiated plasma cells. The presence of B-cell reactive antibodies in AThG results from a thymic inoculum containing a significant percentage of CD20(+) B cells and CD138(+) plasma cells. In this paper, the experimental and clinical evidence supporting the B-cell activity of AThG preparations, and their mechanisms of action, are reviewed.

Animals↗
PubMed2004

Cognitive complexity in response to traumatic experiences.

Two studies examined how personality motives influence the perception of traumatic events in memory and how such perception may be linked to psychological distress. Participants completed implicit and explicit measures of agentic and communal motives. In Study 1, participants living in New York City at the time of the terrorist attacks wrote their thoughts and feelings about the events of September 11th. In Study 2, participants wrote about a personally traumatic experience. In both studies, they also completed questionnaires on psychological symptoms and stress-related growth. The memories were then scored for differentiation and integration. Agentic motives correlated with differentiated perceptions and differentiation was linked to dissociative symptoms in Study 2. Communal motives related to integrated perceptions, and integration related to stress-related growth in both studies. Findings suggest that motives play a significant role in the perception of traumatic and difficult experiences and that these perceptions may be differentially linked to psychological impact.

Cognition↗