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- Buza-Vidas, Natalija, et al.
(författare)
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Delineation of the earliest lineage commitment steps of haematopoietic stem cells: new developments, controversies and major challenges
- 2007
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 14:4, s. 315-321
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review This review addresses recently reported evidence for alternative cellular pathways for haematopoietic stem cell lineage commitment. Recent findings Using various approaches, several laboratories suggested the existence of adult as well as foetal multipotent progenitor cells with combined B cell, T cell and granulocyte/macrophage potential, but little or no megakaryocyte/erythroid potential. Compared with haematopoietic stem cells, these multipotent progenitor cells exhibited downregulated transcriptional expression of genes of the megakaryocyte/erythroid lineages and upregulated expression of lymphoid lineage genes. The existence of these lineage-restricted multipotent progenitor cells suggests that the first lineage commitment step of haematopoietic stem cells does not result in strict separation into myelopoiesis and lymphopoiesis, and that there might be alternative pathways for commitment toward different lineage fates. These findings have been questioned by other studies, however. To resolve this controversy and establish the complete road map for haematopoietic lineage commitment, improved tools and more stringent standards for how to identify and characterize lineage fate options of distinct stem and progenitor cells are needed. Summary Current and future progress in establishing the complete cellular roadmap for haematopoietic lineage commitment will permit identification and characterization of key regulators of lineage fate decisions in haematopoietic stem cells.
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| 2. |
- Hedner, Ulla
(författare)
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Recombinant factor VIIa: its background, development and clinical use.
- 2007
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 14:3, s. 225-229
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review To examine the development of recombinant FVIIa (rFVIIa); a new concept of inducing hemostasis. It was developed for use in hemophilia patients with inhibitors against FVIII or FIX with the vision to provide these patients with a therapeutical option to be used instead of FVIII or FIX. For the first time it was shown that pharmacological doses of FVIIa induced hemostasis. Recent findings Hemostasis was achieved by rFVIIa in major surgery (repeated doses) as well as in a home-treatment setting (one single injection) in severe hemophilia patients with inhibitors. A recent study indicates that rFVIIa may be useful as prophylaxis. In heavily bleeding nonhemophilia patients rFVIIa was shown to induce hemostasis. Pharmacological doses of rFVIIa enhance thrombin generation on activated platelets resulting in the formation of tight hemostatic fibrin plugs resistant against premature proteolysis. High doses of rFVIIa seem to be safe probably due to its localized effect. Summary Pharmacological doses of rFVIIa induce hemostasis in severe hemophilia and in nonhemophilia patients with profuse, heavy bleeding. rFVIIa enhances thrombin generation on activated platelets, thereby initiating the formation of strong, tight fibrin hemostatic plugs resistant to premature lysis. It also seems to be safe in high doses.
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| 5. |
- Storry, Jill
(författare)
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New technologies to replace current blood typing reagents.
- 2007
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 14:6, s. 677-681
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review This review summarizes recent developments in blood grouping and compatibility testing in transfusion medicine. Recent findings Identification of the molecular characteristics of the major human blood groups has provided an opportunity to develop methods for blood group phenotyping using DNA-based technology. Various studies have demonstrated the feasibility of such an approach and have demonstrated the potential to change current procedures for identifying compatible blood, both in routine settings and in highly immunized patients, for whom compatible blood is difficult to obtain. In the obstetric setting, isolation of cell-free DNA from maternal plasma for fetal blood grouping provides a minimally invasive method for determining the risk for haemolytic disease in the newborn. Recombinant technology for synthesizing blood group proteins, although in its infancy, has the potential to change longstanding antibody identification procedures. Summary The molecular revolution occurring throughout medicine is broadly manifest in all areas of transfusion medicine and should contribute to transfusion safety.
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| 6. |
- Yazer, Mark H., et al.
(författare)
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Blood grouping discrepancies between ABO genotype and phenotype caused by O alleles
- 2008
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 15:6, s. 618-624
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review In the modern transfusion service, analysis of the ABO allele underlying a donor or recipient's A or B subtype phenotype is becoming a mainstream adjunct to the serological investigation. Although an analysis of the ABO gene can be helpful in establishing the nature of the subtype phenotype, numerous confounding factors exist that can lead to a discrepancy between the genotype and the observed phenotype. Recent findings Although the most common group O alleles share a common crippling polymorphism, a growing number of alleles feature other polymorphisms that render their protein nonfunctional yet are similar enough to the consensus A allele that an errant phenotype would be predicted from the genotype, if the genotyping method was not specifically designed for their detection. Some of these O alleles might actually encode a protein with weak and variable A antigen synthetic ability. Summary ABO genotyping can be a powerful asset in the transfusion service, but a thorough knowledge of the confounding factors that can lead to genotype/phenotype discrepancies is required.
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