Citations

Abstract After a primary immune response, T cell memory occurs when a subset of Ag-specific T cells resists peripheral selection by acquiring resistance to TCR-induced death. Recent data have implicated Bcl-2 interacting mediator of death (Bim) as an essential mediator of the contraction phase of T cell immunity. In this article, we describe that stromal-derived factor-1α (SDF-1α) ligation of CXCR4 on activated T cells promotes two parallel processes that favor survival, phospho-inactivation of Foxo3A, as well as Bim extralong isoform (BimEL) degradation, both in an Akt- and Erk-dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the proapoptotic effects of TCR ligation or IL-2 deprivation and accumulate cells of a memory phenotype. Unlike SDF-1α, gp120 ligation of CXCR4 has the opposite effect because it causes p38-dependent BimEL upregulation. However, when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α–driven effects of BimEL degradation and acquired resistance to TCR-induced death predominate. These results provide a novel causal link between SDF-1α–induced chemotaxis, degradation of BimEL, and the development of CD4 T cell memory.

We present here a novel case of an atypical Omenn syndrome (OS) phenotype due to mutations in theADAgene encoding adenosine deaminase. This case is noteworthy for a significant increase in circulating CD56brightCD16- cytokine-producing NK cells after treatment with steroids for skin rash.

SummaryBackgroundFunctional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non‐specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive.AimTo present current management options for the treatment of FD (therapeutic gain/response rate noted when available).ResultsThe utility of Helicobacter pylori eradication for the treatment of FD is modest (6–14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7–10% therapeutic gain), histamine‐type‐2‐receptor antagonists (8–35% therapeutic gain), prokinetic agents (18–45%), tricyclic antidepressants (TCA) (response rates of 64–70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies.ConclusionsA reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori‐negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti‐nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.