Ferroportin gene silencing induces iron retention and enhances ferritin synthesis in human macrophages.

Missense mutations in the ferroportin gene (SLC11A3) result in haemochromatosis type 4 [HFE4, Online Mendelian Inheritance in Man (OMIM) reference 606069] or ferroportin disease, an autosomal dominant disorder characterized by predominantly reticuloendothelial iron accumulation. To verify whether HFE4 is caused by defective iron recycling because of loss of functionality of ferroportin, we down-regulated SLC11A gene expression in human macrophages by using small interfering RNAs (siRNAs). Transfection experiments with ferroportin siRNAs resulted in a marked reduction (about two-thirds on average) in ferroportin mRNA levels as detected by quantitative real time polymerase chain reaction.

Hematologic passport for athletes competing in endurance sports: a feasibility study.

Background And Objectives: Strategies based on the use of upper thresholds of hemoglobin or hematocrit to detect blood doping in endurance sports have essentially failed to deter this malpractice. With the aim of establishing a more effective strategy, we analyzed the biological variations of hematologic parameters in professional athletes and investigated the possibility of defining subject-specific reference ranges that could distinguish between physiologic and abnormal variability.

Design And Methods: Hemoglobin concentration, hematocrit, reticulocyte count, serum ferritin and soluble transferrin receptor levels were sequentially evaluated in 923 professional football players.

Abnormal regulation of HFE mRNA expression does not contribute to primary iron overload.

Background And Objectives: Hereditary hemochromatosis (HHC) is a common, recessively inherited, genetic disorder associated with an abnormality of the HFE gene. Subjects homozygous for a point mutation in the gene coding sequence, leading to the amino acid substitution C282Y, are usually affected by the disease. A second point mutation, causing the amino acid substitution H63D, has been described, and compound heterozygotes for the two mutations or homozygotes for the H63D mutation are at risk of developing a milder form of HHC.

Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis.

Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level was related to the degree of iron overload in 20 patients with thalassaemia intermedia, six patients with congenital dyserythropoietic anaemia type II (CDA II) and four patients with X-linked congenital sideroblastic anaemia (XLSA). All but two patients had increased serum ferritin levels (median 601 microgram/l, range 105-2855 microgram/l).

Unbalanced X-chromosome inactivation in haemopoietic cells from normal women.

We studied X-chromosome inactivation patterns in blood cells from normal females in three age groups: neonates (umbilical cord blood), 25-32 years old (young women group) and >75 years old (elderly women). Using PCR, the differential allele methylation status was evaluated on active and inactive X chromosomes at the human androgen receptor (HUMARA) and phosphoglycerate kinase (PGK) loci. A cleavage ratio (CR) > or = 3.

Both cycling and noncycling primitive progenitors continue to be mobilized into the circulation during the leukapheresis of patients pretreated with chemotherapy and G-CSF.

Colony-forming cells (CFC) and long-term culture-initiating cells (LTC-IC) include a spectrum of progenitor types whose potential contributions to the haemopoietic recovery seen in patients transplanted with mobilized peripheral blood progenitor cells (PBPC) remains unclear. We evaluated both the number and cycling status of the circulating LTC-IC and CFC harvested from 12 patients treated with chemotherapy and G-CSF using a modified 6-week LTC-IC assay. The frequency of the LTC-IC and CFC in the mobilized PB samples were increased 45- and 750-fold, respectively.

Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA.

Recent reports have described families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. We have studied the molecular pathogenesis of hyperferritinemia in two families showing different phenotypic expression of this new genetic disorder. Serum ferritin levels ranged from 950 to 1,890 microg/L in affected individuals from family 1, and from 366 to 635 microg/L in those from family 2.