Key Points Cytomegalovirus after bone marrow transplantation remains associated with lower survival but not prevention of leukemia relapse.

The insulin-like growth factor-I receptor (IGF-IR) is a key regulator of cell proliferation and survival. Activation of the IGF-IR induces tyrosine autophosphorylation and the binding of a series of adaptor molecules, thereby leading to the activation of MAPK. It has been demonstrated that pertussis toxin, which inactivates the G i class of GTP-binding proteins, inhibits IGF-I-mediated activation of MAPK, and a specific role for G ␤␥ subunits in IGF-I signaling was shown. In the present study, we have investigated the role of heterotrimeric G i in IGF-IR signaling in neuronal cells. Pertussis toxin inhibited IGF-I-induced activation of MAPK in rat cerebellar granule neurons and NG-108 neuronal cells. G ␣i and G ␤ subunits were associated with IGF-IR immunoprecipitates. Similarly, in IGF-IR-null mouse embryo fibroblasts transfected with the human IGF-IR, G i was complexed with the IGF-IR. G ␣s was not associated with the IGF-IR in any cell type. IGF-I induced the release of the G ␤ subunits from the IGF-IR but had no effect on the association of G ␣i . These results demonstrate an association of heterotrimeric G i with the IGF-IR and identify a discrete pool of G ␤␥ subunits available for downstream signaling following stimulation with IGF-I.Many receptors are coupled to heterotrimeric GTP-binding proteins (G-proteins). Prototypic G-protein coupled receptors (GPCRs) 1 contain a seven-membrane spanning region (1). Activated GPCRs bind to G-proteins and induce the release of G ␤␥ subunits from G ␣ subunits, which allows for the exchange of GDP for GTP on the G ␣ subunit. Activated G i subunits and G ␤␥ heterodimers interact with numerous signaling effectors, including adenylyl cyclase, ion channels, protein kinases, and phospholipases (2-4).In addition to their role in fully differentiated cells, GPCRs have been linked to mitogenesis and development (5-8). A specific role for G i in the induction of mitogenesis has been highlighted by the use of pertussis toxin, which inactivates G i by ADP-ribosylation of the G ␣ subunit. However, G ␣ subunits from several classes of G-proteins are not strongly mitogenic. Rather G ␤␥ heterodimer subunits activate a series of nonreceptor tyrosine kinases, which in turn activates p21 ras and extracellular signal-regulated kinases (or MAPK). Thus, G ␤␥ subunits serve to bridge intracellular signaling of classical GPCRs and mitogenic tyrosine kinase receptors (RTKs).G i also appears to be involved in the mitogenic actions of RTKs. Pertussis toxin variably inhibits the metabolic actions of insulin, both in vitro and in vivo (9 -16), and the insulin receptor may associate with G i (17)(18)(19). Importantly, mice with targeted knockout of G i have defects in insulin signaling (20). EGF-dependent signaling is also impaired by pertussis toxin in rat hepatocytes (21-23) and other cells (24 -27).The insulin-like growth factor-I receptor (IGF-IR), which has strong homology to the insulin receptor, exists as an ␣ 2 -␤ 2 -heterodimer and contains a cytoplasmic tyrosine kinase domain (28, 29). U...

Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.

Respiratory virus infections, such as influenza A, cause significant morbidity in hematopoietic stem cell transplantation (HSCT) recipients. The clinical characteristics and impact of infection with the novel H1N1 virus in this patient population is not yet well defined, however. HSCT recipients diagnosed with proven or probable H1N1 during the 2009 pandemic were identified and charts were retrospectively reviewed with analysis of clinical descriptions, risk factors, diagnosis, treatments, and outcomes. Twenty-seven patients from two medical centers were identified. Fever and cough were the most common presenting symptoms. The incidence of influenza lower respiratory tract infection (LRTI) was 52% (14/27). Compared with patients with LRTI, those with influenza upper respiratory tract infection (URTI) were more likely to have a classic influenza-like syndrome. Compared to patients with URTI, those with LRTI were started on antiviral therapy significantly later after symptom onset (3.0 days vs 6.58 days after onset of symptoms; P = .03; 95% confidence interval [CI], 0.29-6.8). Overall influenza-related 30-day mortality was 22% (6/27), and that in patients with LRTI was 43% (6/14). Chronic steroid use (≥20 mg/day of prednisone equivalent) at the time of presentation was associated with LRTI (P = .006) and mortality (P = .003) on univariate analysis. Five cases were hospital-acquired. In this first season of the novel H1N1 pandemic, infection in HSCT often presented as an atypical severe illness with a high incidence of LRTI and high mortality.

Our findings are the first to demonstrate the modulation of ethanol sensitivity of a tyrosine kinase receptor, and they provide a molecular basis for differential effects of ethanol on cell proliferation.