Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes.

Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs).

Clinical pharmacology of oncology agents in older adults: A comprehensive review of how chronologic and functional age can influence treatment-related effects.

Unique challenges exist when managing older adults with cancer. Associations between cancer and age-related physiologic changes have a direct impact on pharmacokinetics and pharmacodynamics of cancer therapies and can affect drug dosing, dose intensity, efficacy, safety and quality of life. The breadth and depth of these issues, however, have not been fully evaluated because the majority of clinical trials have focused on a younger and healthier population.

Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help.

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6 follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent.

The BCL6 RD2 domain governs commitment of activated B cells to form germinal centers.

To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2(MUT) mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2(MUT) antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells.

Comparison of GE Centricity Electronic Medical Record database and National Ambulatory Medical Care Survey findings on the prevalence of major conditions in the United States.

The study objective was to facilitate investigations by assessing the external validity and generalizability of the Centricity Electronic Medical Record (EMR) database and analytical results to the US population using the National Ambulatory Medical Care Survey (NAMCS) data and results as an appropriate validation resource. Demographic and diagnostic data from the NAMCS were compared to similar data from the Centricity EMR database, and the impact of the different methods of data collection was analyzed. Compared to NAMCS survey data on visits, Centricity EMR data shows higher proportions of visits by younger patients and by females.

Prevalence of obesity, type II diabetes mellitus, hyperlipidemia, and hypertension in the United States: findings from the GE Centricity Electronic Medical Record database.

This study analyzed GE Centricity Electronic Medical Record (EMR) data to examine the effects of body mass index (BMI) and obesity, key risk factor components of metabolic syndrome, on the prevalence of 3 chronic diseases: type II diabetes mellitus, hyperlipidemia, and hypertension. These chronic diseases occur with high prevalence and impose high disease burdens. The rationale for using Centricity EMR data is 2-fold.