Biomedical subjects

Brian P O'Connor

Publications and source records attributed to Brian P O'Connor.

14 recordsLinked to original sources

PubMed2006

Imprinting the fate of antigen-reactive B cells through the affinity of the B cell receptor.

Long-lived plasma cells (PCs) and memory B cells (B(mem)) constitute the cellular components of enduring humoral immunity, whereas short-lived PCs that rapidly produce Ig correspond to the host's need for immediate protection against pathogens. In this study we show that the innate affinity of the BCR for Ag imprints upon naive B cells their differentiation fate to become short- or long-lived PCs and B(mem). Using BCR transgenic mice with varying affinities for Ag, naive B cells with high affinity lose their capacity to form germinal centers (GCs), develop neither B(mem) nor long-lived PCs, and are destined to a short-lived PC fate. Moderate affinity interactions result in hastened GC responses, and differentiation to long-lived PCs, but B(mem) remain extinct. In contrast, lower affinity interactions show tempered GCs, producing B(mem) and affinity-matured, long-lived PCs. Thus, a continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity.

Adoptive Transfer↗

PubMed2006

Cutting edge: rho activation and actin polarization are dependent on plexin-A1 in dendritic cells.

We recently identified expression of the semaphorin receptor, plexin-A1, in dendritic cells (DCs); however, its function in these cells remains to be elucidated. To investigate function and maximize physiological relevance, we devised a retroviral approach to ablate plexin-A1 gene expression using small hairpin RNA (shRNA) in primary bone marrow-derived DCs. We show that plexin-A1 localizes within the cytoplasm of immature DCs, becomes membrane-associated, and is enriched at the immune synapse in mature DCs. Reducing plexin-A1 expression with shRNA greatly reduced actin polarization as well as Rho activation without affecting Rac or Cdc42 activation. A Rho inhibitor, C3, also reduced actin polarization. These changes were accompanied by the near-ablation of T cell activation. We propose a mechanism of adaptive immune regulation in which plexin-A1 controls Rho activation and actin cytoskeletal rearrangements in DCs that is associated with enhanced DC-T cell interactions.

Actin Depolymerizing Factors↗

PubMed2006

SPSS and SAS programs for generalizability theory analyses.

The identification and reduction of measurement errors is a major challenge in psychological testing. Most investigators rely solely on classical test theory for assessing reliability, whereas most experts have long recommended using generalizability theory instead. One reason for the common neglect of generalizability theory is the absence of analytic facilities for this purpose in popular statistical software packages. This article provides a brief introduction to generalizability theory, describes easy to use SPSS, SAS, and MATLAB programs for conducting the recommended analyses, and provides an illustrative example, using data (N = 329) for the Rosenberg Self-Esteem Scale. Program output includes variance components, relative and absolute errors and generalizability coefficients, coefficients for D studies, and graphs of D study results.

Electronic Data Processing↗

PubMed2005

A search for consensus on the dimensional structure of personality disorders.

Previous attempts to elucidate the dimensional structure of personality disorders (PDs) have been based on single samples and measures. Like one-item tests, they are useful but scattered and potentially misleading glimpses at the true structure of PDs. Therefore, reanalyses of 33 previously published data sets were conducted using recommended statistical procedures to arrive at consensus structures. Similar reanalyses of published data were conducted on associations between PDs and the five-factor model of normal personality characteristics. High degrees of congruence were observed between the consensus PD structures and the consensus structures suggested by dimensions of normal personality. The analytic techniques used in the present study helped bypass methodological problems inherent in previous tests and revealed higher levels of support for both theoretically and empirically based representations of the five-factor model approach to PDs.

Consensus↗

PubMed2004

BCMA is essential for the survival of long-lived bone marrow plasma cells.

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this alpha-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor-immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA-/- mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.

Animals↗

PubMed2004

Physical exercise and experienced bodily changes: the emergence of benefits and limits on benefits.

Self-reports of levels of physical exercise, experienced bodily changes, and attitudinal and well-being variables were obtained from 407 adults, aged 26 to 95 years. The purpose was to assess the relative magnitudes of the experienced benefits of exercise across the exercise continuum. Cluster analyses identified three groups at each of four age levels: a) sedentary people who experienced negative bodily changes; b) modest exercisers who reported the most positive bodily changes; and c) high exercisers who reported only minimal bodily changes. Psychological barriers to exercise among sedentary people included negative exercise attitudes, attributions of negative bodily changes to aging, and low levels of exercise motivation and self-efficacy. Modest and high exercisers both scored high on attitude and well-being variables.

Adult↗

PubMed2004

Older persons' perceptions of the frequency and meaning of elderspeak from family, friends, and service workers.

Older persons (N = 159) were surveyed for their impressions of and experiences with elderspeak from friends, same-age family members, younger family members, familiar service workers, and unfamiliar service workers. Two dimensions, "warmth" and "superiority," emerged in the judgments of elderspeak from all five speaker types. Respondents perceived more warmth and less superiority in elderspeak from friends than they did in elderspeak from unfamiliar service workers. Among younger seniors, elderspeak was received primarily from unfamiliar service workers, whereas among nursing home residents, elderspeak was received from all speaker types. Variation thus exists in the covert experiences of elderspeak from different sources, and in the frequency of receipt of elderspeak from different sources.

Aged↗

PubMed2004

SPSS and SAS programs for addressing interdependence and basic levels-of-analysis issues in psychological data.

Levels-of-analysis issues arise whenever individual-level data are collected from more than one person from the same dyad, family, classroom, work group, or other interaction unit. Interdependence in data from individuals in the same interaction units also violates the independence-of-observations assumption that underlies commonly used statistical tests. This article describes the data analysis challenges that are presented by these issues and presents SPSS and SAS programs for conducting appropriate analyses. The programs conduct the within-and-between-analyses described by Dansereau, Alutto, and Yammarino (1984) and the dyad-level analyses described by Gonzalez and Griffin (1999) and Griffin and Gonzalez (1995). Contrasts with general multilevel modeling procedures are then discussed.

Analysis of Variance↗

PubMed2003

The rise and fall of long-lived humoral immunity: terminal differentiation of plasma cells in health and disease.

Long-lived humoral immune responses are a hallmark of thymus-dependent immunity. The cellular basis for enduring antibody-mediated immunity is long-lived memory B cells and plasma cells (PCs). Both of these cell populations acquire longevity as a result of antigen-specific, CD40-dependent, cognate interactions with helper T cells within germinal centers (GCs). At the molecular level, defined functional domains of CD40 control the post-GC fate of B cells. PC precursors that emerge from these GC reactions are highly proliferative and terminally differentiate to end-stage cells within the bone marrow (BM). The striking phenotypic similarities between the PC precursors and the putative malignant cell in multiple myeloma (MM) suggests that MM may result from the transformation of PC precursors. Within the domain of autoimmune disease, recent studies have shown that dysregulated migration of PCs to the BM may impact immune homeostasis and the development of lupus. Understanding the processes of normal PC differentiation will provide strategic insights into identifying therapeutic targets for the treatment of differentiated B-cell disorders.

Animals↗

PubMed2002

Short-lived and long-lived bone marrow plasma cells are derived from a novel precursor population.

The contribution that long-lived bone marrow (BM) plasma cells (PCs) provide to enduring humoral immunity has been underscored by a number of recent studies. However, little is known about the immediate precursors that give rise to long-lived PCs in the BM of immune individuals. We have identified subsets of antigen-experienced B cells within the immune BM that are precursors to PCs. These PC precursors arise in the BM 14 days after immunization and persist for greater than 9 months. Phenotypically distinct subsets of PC precursors give rise to short-lived or long-lived PCs. The differentiation of PC precursors to PCs occurs in the absence of antigen and requires cell division. The functional significance of these newly identified PC precursors in the persistence and quality of the humoral immune response is discussed.

Animals↗

PubMed2002

Police officer job satisfaction in relation to mood,well-being, and alcohol consumption.

The authors examined job satisfaction, job stress, and thoughts of quitting in relation to positive and negative affect, life satisfaction, self-esteem, and alcohol consumption among police officers. Exploratory and confirmatory factor analyses revealed that 2 dimensions, positive affect and negative affect, provided a clear family-tree organizational framework for representing the otherwise confusing pattern of associations between job and well-being variables. Job satisfaction was primarily associated with positive affect, life satisfaction, and self-esteem; job stress was primarily associated with negative affect and alcohol consumption; thoughts of quitting had moderate loadings on both factors. The 2-dimensional framework may prove useful as a guide in reviewing research in this field and in selecting constructs and measures for inclusion in future research.

Adaptation, Psychological↗

PubMed2002

Short-circuiting long-lived humoral immunity by the heightened engagement of CD40.

Agonistic alpha CD40 Ab's have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can be dramatically altered. These are the first studies to describe the multifaceted function of CD40 in determining the fate of antigen-reactive B cells and provide novel insights into how CD40 agonists can short-circuit humoral immunity.

Animals↗

PubMed2002

A quantitative review of the comprehensiveness of the five-factor model in relation to popular personality inventories.

Reports of associations between the five-factor model (FFM) and the scales of popular personality inventories have generated controversy regarding the comprehensiveness of the FFM. The controversy is fueled by a preoccupation with capturing scale variance and differentiating between specific scales, whereas the focus should instead be on whether the FFM captures the common variance and the dimensions that exist in personality constructs. Analyses of published data revealed that the portions of scale variance captured by the FFM (mean = 38%) were substantial when evaluated in relation to the portions of common variance that exist in most personality inventories (mean = 50%). Furthermore, interbattery factor analyses indicated that the factor structures in most personality inventories can be closely replicated using data derived solely from scale associations with the FFM. Exceptions to this finding occurred for only 2 of 28 personality inventories. The findings support the comprehensiveness of the FFM.

Factor Analysis, Statistical↗

PubMed2002

The search for dimensional structure differences between normality and abnormality: a statistical review of published data on personality and psychopathology.

A statistical review of published data for 37 personality and psychopathology inventories was conducted to determine whether there are dimensional structure differences between clinical and nonclinical respondents. Correlation and factor-loading matrices from multiscale inventories and from specialized measures were tested for structural invariance across populations. There was relatively consistent evidence for high levels of similarity between normal and abnormal populations both in the number of factors that exist in the data matrices and in the factor patterns. The dimensional universes of normality and abnormality are apparently the same, at least according to data derived from contemporary assessment instruments. Categorical-taxonic differences between clinical and nonclinical populations, which were not examined, may nevertheless exist within contexts of dimensional structure similarity.

Factor Analysis, Statistical↗