Would You Be Surprised if This Patient Died in the Next 12 Months? Using the Surprise Question to Increase Palliative Care Consults From the Emergency Department.

Background: There is a growing movement to increase palliative care consults from the emergency department (ED) to reduce healthcare costs and improve quality of life. The surprise question is a screening tool that emergency medicine physicians may be able to use towards achieving this goal.

Objective: The objectives of this study were to increase awareness of hospice and palliative care medicine (HPM) among emergency medicine (EM) providers and to evaluate whether this heightened awareness increased palliative care consults among participating emergency medicine providers.

CD23 regulates monocyte activation through a novel interaction with the adhesion molecules CD11b-CD18 and CD11c-CD18.

CD23 is expressed on a variety of haemopoietic cells and displays pleiotropic activities in vitro. We report that in addition to CD21 and IgE, CD23 interacts specifically with the CD11b and CD11c, the alpha chains of the beta 2 integrin adhesion molecule complexes CD11b-CD18 and CD11c-CD18, on monocytes. Full-length recombinant CD23 incorporated into fluorescent liposomes was shown to bind to COS cells transfected with cDNA encoding either CD11b-CD18 or CD11c-CD18 but not with CD11a-CD18.

Evidence for a role of Fc epsilon RII/CD23 in the IL-4-induced nitric oxide production by normal human mononuclear phagocytes.

IL-4 stimulates NO production by human monocytes. After 6 days of culture with IL-4, human monocytes released detectable amounts of nitrite and L-citrulline that were inhibited in the presence of nitro-L-arginine (1 mM). Incubation with an anti-CD23 mAb Fab fragment that suppressed the biological effect of CD23 led to a strong reduction (50 to 70%) of the IL-4-induced nitrite and L-citrulline production.

IL-4 induces cAMP and cGMP in human monocytic cells.

Human monocytes, preincubated with IFN-gamma respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 - 3 min) and cAMP (20 - 25 min) in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors.

Ligation of CD23 activates soluble guanylate cyclase in human monocytes via an L-arginine-dependent mechanism.

Transduction through Fc epsilon R2/CD23 was analyzed in normal human monocytes using immunoglobulin E (IgE)-anti-IgE immune complexes (IgE ICs) and monoclonal antibodies (mAbs) to CD23. Anti-CD23 mAb and IgE IC triggered a time-dependent increase in cGMP and cAMP in interleukin-4-preincubated (CD23+) but not in unstimulated (CD23-) monocytes. Maximal cGMP and cAMP accumulations were observed 10 and 20 min, respectively, after the onset of CD23 ligation.

Role of cyclic nucleotides and nitric oxide in blood mononuclear cell IgE production stimulated by IL-4.

The involvement of cyclic nucleotides and of phosphodiesterase activities in IL-4-induced IgE production and release of the soluble form of the low affinity receptor for IgE (sCD23) by normal human peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were stimulated by a suboptimal dose of IL-4 (10 ng/ml) cAMP inducers, adrenaline (ADR) and cholera toxin (CTx), which were found to potentiate IL-4-induced IgE production and sCD23 release after 12 days of culture. In the presence of an optimal dose of IL-4 (30 ng/ml), both ADR and CTx inhibited the production of both IgE and sCD23.

Modulation by interleukin-4 of cytokine release from mononuclear phagocytes in asthma.

Background: Interleukin (IL)-4 is involved in IgE upregulation and downregulates cytokine release by mononuclear phagocytes. Mononuclear cells release greater amounts of IL-1, tumor necrosis factor-alpha, and IL-6 in patients with asthma than in control subjects, but the effect of IL-4 on cells from patients with asthma is unknown. The effects of IL-4 on the release of IL-1, tumor necrosis factor-alpha, and IL-6 by monocytes and alveolar macrophages were compared in 19 patients with asthma and 18 control subjects.

Growth arrest and terminal differentiation of leukemic myelomonocytic cells induced through ligation of surface CD23 antigen.

Acute myelogenous leukemia (AML) cells express CD23 surface antigen after in vitro treatment with various cytokines, including interleukin-4 (IL-4) and interferon gamma. Subsequent ligation of CD23 by specific monoclonal antibody (MoAb) induces substantial morphologic and functional modifications in these cells. In the present study, we investigated the role of CD23 in the proliferation and the maturation of leukemic cells from AML patients or the U937 cell line.

[Role of interleukin-4 in the regulation of nitric oxide production by normal human monocytes].

Resting normal human monocytes were found to produce small amounts of cGMP in response to IL-4. This production was inhibited in the presence of LNMMA suggesting an association with activation of the NO synthase (NOS) pathway. In addition, this cGMP generation was abrogated in the presence of either a Ca2+ chelator, EGTA, or a calcium/calmodulin inhibitor, W7, suggesting that IL-4 stimulates the constitutive NOS (cNOS).

Phenotypic and functional modulation of normal human alveolar macrophages by histamine.

Alveolar macrophages (AM) play a regulatory role in asthma. AM from asthmatics are activated, release increased amounts of cytokines, and express higher levels of the low affinity receptor for IgE (Fc epsilon RIIb/CD23b) and receptors for adhesion molecules. The bronchial microenvironment may modulate the phenotypic and functional characteristics of AM.

Regulatory role of nitric oxide in the IL-4-induced IgE production by normal human peripheral blood mononuclear cells.

An in vitro study was performed in order to assess a possible regulatory role of nitric oxide (NO), a short-lived biologic mediator that displays immunoregulatory properties, in the IL-4-driven synthesis of IgE by normal human peripheral blood mononuclear cells (PBMC). In addition to induce IgE production, IL-4 was found to elicit nitrite (NO2-) release by PBMC. A marked correlation was observed between IgE secretion and nitrite release by PBMC stimulated with an optimal concentration of IL-4.

Heterogenous nitrite production by IL-4-stimulated human monocytes and peripheral blood mononuclear cells.

The capacity of human peripheral blood mononuclear cells and monocytes to generate nitrites, spontaneously or in response to Interleukin-4 was evaluated in vitro. Peripheral blood mononuclear cells and monocytes were found to release significant amounts of nitrites after 8 to 12 days in culture. This spontaneous production of nitrites was inhibited in the presence of 1 mM NG monomethyl-L-arginine, suggesting that this process was dependent upon the L-arginine metabolism.

Heterogeneous spontaneous and interleukin-4-induced nitric oxide production by human monocytes.

The generation of nitric oxide by human monocytes has long been a subject of controversy because of the difficulty of rationalizing this production. In this work we evaluated the capacity of human monocytes to produce nitric oxide (NO) as measured by nitrite (NO2-) release. Resting unstimulated monocytes (2 x 10(6) cells/ml) were found to produce significant amounts of NO2- after 8 to 12 days in culture.

Involvement of Fc epsilon RII/CD23 and L-arginine-dependent pathway in IgE-mediated stimulation of human monocyte functions.

Elevated IgE levels are commonly observed during the inflammatory responses in allergy and a variety of infections. This Ig activates the release of multiple mediators from monocytes/macrophages. In the present work, we attempted to clarify the IgE-dependent events involved in the activation of monocyte functions.

Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.

Interleukin 4 (IL-4)-induced IgE production by normal peripheral blood mononuclear cells (PBMC) and E- cells (PBMC partially depleted of T cells) was significantly enhanced by leukotriene B4(LTB4) in a dose-dependent manner, whereas LTB4 by itself was not effective for IgE production. The potentiating effect of LTB4 was strictly dependent on IL-4. When PBMC or E- cells were primed with IL-4 (300 U/ml) for 48 hr, then recultured with LTB4 alone (10(-10) to 10(-8) M), increased IgE production was observed.

Involvement of cyclic AMP and nitric oxide in immunoglobulin E-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast cells, macrophages, fibroblasts) during wounding, cutaneous allergy, and infections. We have previously demonstrated that after stimulation with interleukin 4 or interferon-gamma, human EK express the low-affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody induces a dose-dependent release of interleukin 6 and tumor necrosis factor-alpha from EK.

Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes. Involvement of the nitric oxide synthase pathway.

Resting human blood monocytes from some donors were found to produce a small amount of 3'-5' guanine cyclic monophosphate (cGMP) in response to interleukin 4 (IL-4). A much higher response was observed when monocytes were preincubated with interferon (IFN-gamma), which alone was ineffective. Preincubation of monocytes with IL-4 led, in contrast, to their subsequent incapacity to generate cGMP in response to IL-4.

Beta 2-adrenoceptor agonists regulate the IL-4-induced phenotypical changes and IgE-dependent functions in normal human monocytes.

The beta 2-adrenoceptor agonists salbutamol and fenoterol were tested for their regulatory effects on human monocyte phenotype and functions, either alone or in combination with interleukin-4 (IL-4). These drugs enhanced in a dose-dependent manner the IL-4-induced membrane and mRNA expression of the low-affinity receptor for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form, sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic beta 2-chain (CD18) of the leukocyte functional antigen (LFA1) family.

CD23 and IgE expression during the human immune response to cutaneous leishmaniasis: possible role in monocyte activation.

Leishmania brasiliensis causes cutaneous leishmaniasis (CL) in humans. During this infection, a variety of inflammatory mediators are produced by T cells and monocytes/macrophages. In the present study, we analysed serum IgE levels and their correlation with in situ expression of the low affinity receptor for IgE (Fc epsilon RII/CD23) in patients infected with L.

[Physiopathological role of low affinity IgE receptor (CD23) in hematopoietic cells].

Ligation of the low affinity IgE receptor by specific monoclonal antibodies or multivalent IgE complexes result in the transduction of signals which differ according to the CD23 isotype expressed by the various cell types. In B lymphocytes, it elicits the early activation of phospholipase C through a mechanism involving a G-protein insensitive to Pertussis toxin, followed by a late phase of cAMP accumulation. In monocytes, which express the CD23b isoform, ligation of CD23 was also found to induce a delayed accumulation of cAMP, that was largely dependent on a prior cGMP increase through a mechanism involving the activation of a NO synthase.

Biochemical and functional alterations induced by CD23 ligation in the human promonocytic cell line U937.

The early events triggered in interleukin-4 (IL-4)-stimulated U937 cells by ligation of CD23/Fc epsilon RII with specific monoclonal antibodies (mAb) were analysed, as a model of the action of this molecule on the differentiation of promonocytic cells. As well as IL-4-activated human monocytes, addition of anti-CD23 mAb to IL-4-treated U937 cells triggered cAMP accumulation but did not evoke significant polyphosphoinositide hydrolysis. However, by a microspectrofluorometric technique allowing single cell analysis, anti-CD23 mAb was found to elicit calcium mobilization in these cells.

Maturation of human myelomonocytic leukemia cells following ligation of the low affinity receptor for IgE (Fc epsilon RII/CD23).

The regulation of the low affinity receptor for IgE (Fc epsilon RII/CD23) expression and its role were investigated in U937 cell line and in leukemic cells from a patient (Amb) with acute myeloblastic leukemia. Both cell populations were CD23- but could acquire CD23 expression following treatment with IL-4. CD23+ cells, however, remained blastic and did not show any significant phenotypical and functional modifications.

Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes.

The low affinity IgE receptor CD23 may play a role in several B lymphocyte functions, such as cell activation and multiplication, Ag presentation, and IgE production. We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein. In our work, we show that anti-CD23 mAb elicit an increase in cAMP concentration in human peripheral blood-derived B lymphocytes.

Beta 2-adrenoceptor stimulation augments the IL-4-induced CD23 expression and release and the expression of differentiation markers (CD14, CD18) by the human monocytic cell line, U 937.

The effect of beta 2-adrenoceptor agonists and interleukin-4 (IL-4) on the CD23 expression on, and release from, the human promonocytic cell line, U 937, was investigated. As assessed by flow cytometry, incubation of U 937 cells in the presence of salbutamol, fenoterol or IL-4 induced a concentration- and time-dependent increase in CD23 expression, that was maximal after 48 hr and followed by a decrease thereafter. In addition, salbutamol potentiated the effect of IL-4, the optimal concentration of the drug being a function of the concentration of this cytokine.

Functional interaction between beta 2-adrenoceptor agonists and interleukin-4 in the regulation of CD23 expression and release and IgE production in human.

Normal human peripheral blood mononuclear cells (PBMC) produced IgE when stimulated with IL-4. In the present report it was shown that beta 2-adrenoceptor agonists, salbutamol and fenoterol, potentiated the IL-4-induced IgE production without significantly affecting the expression of the low affinity receptor for IgE at the cell surface of monocytes and B lymphocytes. However, beta 2-adrenoceptor agonists were shown to enhance at day 7 the IL-4-induced release of the soluble form of CD23 (sCD23) by PBMC.