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- Borregaard, N, et al.
(author)
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Regulation of human neutrophil granule protein expression
- 2001
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In: Current Opinion in Hematology. - 1531-7048. ; 8:1, s. 23-27
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Journal article (peer-reviewed)abstract
- The function of the mature polymorphonuclear neutrophil is dependent on its granules, each with its characteristic content of proteins. The granule proteins are formed at different stages during maturation of neutrophils from myeloblasts to segmented cells. The regulation of granule protein expression is controlled by a number of transcription factors, many of which are also essential for commitment of multipotent hematopoietic stem cells to lineage-committed myeloid progenitor cells and for differentiation of these progenitor cells; among these, PU.1 and C/EBPalpha stand out as critical for all granule proteins whereas AML-1 is critical for primary granule protein expression and C/EBPepsilon for secondary and tertiary granule protein expression.
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- Buza-Vidas, Natalija, et al.
(author)
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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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In: Current Opinion in Hematology. - 1531-7048. ; 14:4, s. 315-321
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Journal article (peer-reviewed)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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- Hedner, Ulla
(author)
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Recombinant factor VIIa: its background, development and clinical use.
- 2007
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In: Current Opinion in Hematology. - 1531-7048. ; 14:3, s. 225-229
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Journal article (peer-reviewed)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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- Karlsson, Christine, et al.
(author)
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RNA interference screening to detect targetable molecules in hematopoietic stem cells.
- 2014
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In: Current Opinion in Hematology. - 1531-7048. ; 21:4, s. 283-288
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Research review (peer-reviewed)abstract
- The molecular principles regulating hematopoietic stem cells (HSCs) remain incompletely defined. In this review, we will discuss how RNA interference (RNAi) screening has emerged as a new and powerful tool to molecularly dissect various functional aspects of both normal and malignant HSCs, and how this may ultimately enable the discovery of novel therapeutic targets for clinical applications.
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- Kjeldsen-Kragh, Jens, et al.
(author)
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Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune thrombocytopenia.
- 2012
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In: Current Opinion in Hematology. - 1531-7048. ; 19:6, s. 469-474
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Journal article (peer-reviewed)abstract
- PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
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