A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis.
Background. Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population.Methods. We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03 A -adjuvanted H1N1v vaccine containing 3.75 lg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 lg HA to assess hemagglutination inhibition (HI) response and safety.Results. A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers $1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n 5 155) and in 75.5% in the nonadjuvanted group (B group) (n 5 151) (P , .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers $1:40 (P 5 .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD41 cell count or viral load has been detected.Conclusions. In HIV-1-infected adults, the AS03 A -adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.Two large studies performed before the era of highly active antiretroviral therapy (HAART) evidenced high numbers of hospital admissions and high mortality related to seasonal influenza in human immunodeficiency virus (HIV)-infected patients [1,2]. In the post-HAART era, the number of
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