Murine Glucocorticoid Receptors Orchestrate B Cell Migration Selectively between Bone Marrow and Blood.

Glucocorticoids promote CXCR4 expression by T cells, monocytes, macrophages, and eosinophils, but it is not known if glucocorticoids regulate CXCR4 in B cells. Considering the important contributions of CXCR4 to B cell development and function, we investigated the glucocorticoid/CXCR4 axis in mice. We demonstrate that glucocorticoids upregulate CXCR4 mRNA and protein in mouse B cells. Using a novel strain of mice lacking glucocorticoid receptors (GRs) specifically in B cells, we show that reduced CXCR4 expression associated with GR deficiency results in impaired homing of mature B cells to bone marrow, whereas migration to other lymphoid tissues is independent of B cell GRs. The exchange of mature B cells between blood and bone marrow is sensitive to small, physiologic changes in glucocorticoid activity, as evidenced by the lack of circadian rhythmicity in GR-deficient B cell counts normally associated with diurnal patterns of glucocorticoid secretion. B cellGRKO mice mounted normal humoral responses to immunizations with T-dependent and T-independent (Type 1) Ags, but Ab responses to a multivalent T-independent (Type 2) Ag were impaired, a surprise finding considering the immunosuppressive properties commonly attributed to glucocorticoids. We propose that endogenous glucocorticoids regulate a dynamic mode of B cell migration specialized for rapid exchange between bone marrow and blood, perhaps as a means to optimize humoral immunity during diurnal periods of activity.

Macrothrombocytopenia With Döhle Body-Like Granulocyte Inclusions: A Case Report of May-Hegglin Anomaly in a 33-Year-Old White Woman With an Update on the Molecular Findings of MYH9-Related Disease.

A 33-year-old white woman arrived at the hospital to undergo a hysterectomy due to uterine fibroids. Blood smear review identified macrothrombocytopenia and Döhle body-like cytoplasmic leukocyte inclusions. Genetic testing identified a mutation in exon 39 of the myosin heavy chain gene (MHY9; OMIM 160775), which confirmed the diagnosis of May-Hegglin anomaly. May-Hegglin anomaly is one of a spectrum of MYH9 disorders that also includes Sebastian, Epstein, and Fechtner syndromes. Herein, we describe the clinical and laboratory presentation of a patient with May-Hegglin anomaly and provide an update on the molecular findings and a discussion of the genotypic-phenotypic correlations in this potentially underdiagnosed disorder.

Analysis of glucocorticoid receptors and their apoptotic response to dexamethasone in male murine B cells during development.

Glucocorticoids have an important role in the resolution of inflammation and clinically they are routinely used to treat allergies, asthma, sepsis, and autoimmune diseases. In addition, glucocorticoids are well recognized to negatively impact the development and function of T cells in the immune system by inducing apoptosis. Less is known however about glucocorticoid function in B lymphocytes. Herein, we demonstrate that the glucocorticoid receptor (GR) is present in B-cell populations isolated from both the spleen and the bone marrow. B-cell populations were found to express more GR than non-B-cell populations from both the spleen and the bone marrow. GR protein was found in all B-cell (B220+) developmental subsets (Mature IgM+IgD+, Immature IgM+IgD-, and Pro/Pre IgM-IgD-) isolated from spleen. GR staining intensity was varied among the B-cell developmental subsets and was found to be higher in B cells isolated from the spleen (secondary lymphoid organ) versus the bone marrow (primary lymphoid organ). Ex vivo cell culture of murine splenocytes and bone marrow lymphocytes indicated that dexamethasone stimulated apoptosis in all B-cell developmental subsets demonstrating glucocorticoid responsiveness. Furthermore, in vivo administration of dexamethasone to adrenalectomized mice reduced B-cell numbers in both spleen and bone marrow. These data suggest that glucocorticoid signaling has an important understudied role in B-cell life-or-death decisions.

Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword.

First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.

Introduction of a new observation chart and education programme is associated with higher rates of vital-sign ascertainment in hospital wards.

INTRODUCTION Local and national awareness of the need to improve the recognition and response to the clinical deterioration of hospital inpatients is high. The authors designed and implemented a programme to improve recognition of deteriorating patients in their hospital; a new observation chart for vital signs was one of the major elements. The aim of the study is to evaluate the impact of the new chart and associated education programme on the completeness of vital-sign recording in ward areas. METHODS The setting is a university-affiliated teaching hospital in Sydney, Australia. Three study periods, each lasting 14 days (preintervention, 2 weeks postintervention, 3 months postintervention), were carried out in three wards. The new observation chart was supported by an education programme. The primary outcome measures were the ascertainment rates of individual vital signs as a proportion of total observation sets. RESULTS Documentation of respiratory rate increased from 47.8% to 97.8% (p<0.001) and was sustained at 3 months postintervention (98.5%). Collection of a full set of vital signs also improved by a similar magnitude. Basic neurological observation for all patients was introduced in the new chart; the uptake of this was very good (93.1%). Ascertainment rates of blood pressure and oxygen saturation also increased by small but significant amounts from good baseline rates of 97% or higher. CONCLUSION The introduction of a new observation chart, and education regarding its use and importance, was associated with a major improvement in the recording of respiratory rate and other vital signs.