Background-Peripheral blood CD34ϩ cells and circulating endothelial progenitor cells (EPCs) increase in myocardial infarction and vascular injuries as a reflection of endothelial damage. Despite the occurrence of endothelial dysfunction in heart failure (HF), no data are available on EPC mobilization in this setting. We investigated the pattern of CD34
The P2X7R is an ATP-gated cation channel expressed in hemopoietic cells that participates in both cell proliferation and apoptosis. Expression and function of the P2X7R have been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL). Functional variants causing loss-of-function of the P2X7R have been identified, namely, polymorphisms 1513A>C (E496A), 1729T>A (I568N), and 946G>A (R307Q). Here we investigated other nonsynonymous polymorphisms located either in the extracellular portion of the receptor, such as the 489C>T (H155Y) variant, or in the long cytoplasmic tail of the receptor, such as the 1068G>A (A348T), 1096C>G (T357S), and 1405A>G (Q460R) variants. P2X7R function was monitored by measuring ATP-induced Ca2+ influx in PBL of patients affected by CLL and in recombinant human embryonic kidney (HEK) 293 cells stably transfected with each single P2X7 allelic variant. Ca2+ influx was markedly reduced in association with the 1513C allele, whereas variants located in the same intracellular domain, such as the 1068A, 1096G, or 1405G variants, were associated with a minor functional decrease. Significant Ca2+ flux increase was observed in lymphocytes from CLL patients bearing the 489C/T and 489T/T genotypes in association with the 1513A/A genotype. Functional analysis in recombinant HEK293 cells expressing P2X7R confirmed an increased ATP-dependent activation of the P2X7 489T mutant with respect to the wild type receptor, as assessed by both by [Ca2+]i influx and ethidium uptake experiments. These data identify the 489C>T as a gain-of-function polymorphism of the P2X7R.
Summary. Effects of epoetin alfa on transfusions, haemoglobin (Hb) and quality of life (QOL) were evaluated in a placebo-controlled study of 145 patients with multiple myeloma and anaemia (Hb , 11 g/dl). During the 12-week, double-blind phase, patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly; the dose (or volume) was doubled at week 4 if Hb response was inadequate. Patients completing this phase could enter the subsequent optional 12-week phase of open-label epoetin alfa treatment. During double-blind treatment, epoetin alfa significantly decreased the incidence of transfusion compared with placebo (28% vs. 47%, P 0´017), regardless of patients' transfusion history, and increased mean Hb (1´8 g/dl vs. 0´0 g/dl, P , 0´001). Univariate analysis showed significant (P # 0´05) improvement in more QOL measures with epoetin alfa than with placebo; multivariate analysis discerned no between-treatment differences. Significantly (P 0´038) more epoetin alfa vs. placebo patients had improved performance scores. At the end of the open-label treatment phase, patients who had continued epoetin alfa maintained Hb status, and placebo patients who were switched to epoetin alfa had mean Hb increases of 2´4 g/dl. Adverse events were similar between treatment groups. Epoetin alfa proved effective and well tolerated for treating anaemia in patients with multiple myeloma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.