| 2771. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation
- 2004
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 125, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis. Platelet-induced extracellular phosphorylation of plasma proteins suggests that this is due to persistent activation of the platelets. We examined 30 SLE patients (15 with thrombotic disease), 18 non-SLE patients with deep vein thrombosis (DVT) and 50 healthy controls by analysing beta-thromboglobulin, activated factor XI-antithrombin complexes and fibrinogen-bound phosphate. All parameters were elevated in SLE patients, particularly those with thrombosis, but normal in DVT cases and healthy controls. We conclude that thrombotic disease in SLE patients is associated with a persistent systemic platelet activation that may lower the threshold for induction of thrombosis.
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| 2772. |
- Nilsson, I. M., et al.
(författare)
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Suppression of Secondary Antibody Response by Intravenous Immunoglobulin in a Patient with Haemophilia B and Antibodies
- 1983
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Ingår i: Scandinavian Journal of Haematology. - : Wiley. - 0036-553X. ; 30:5, s. 458-464
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Tidskriftsartikel (refereegranskat)abstract
- A 39‐year‐old patient, suffering from severe haemophilia B and antibodies against factor IX, has twice been treated with extracorporeal protein A‐Sepharose adsorption followed by conventional substitution therapy in combination with immunosuppression (cyclophos‐phamide). On both occasions, separated by a 2‐year interval, the same procedure was followed except that, on the second, administration of i.v. immunoglobulin (Gammonativ, KabiVitrum) was added. Within a week of the first treatment the patient developed a 15‐fold increase in the antibody titre. Following the second treatment described here, no secondary antibody response could be detected, and after a further 12 weeks only traces of antibodies are demonstrable. It seems that antibody synthesis was suppressed by the i.v. immunoglobulin. No evidence was found to demonstrate that the effect was due either to a non‐specific suppression of the immune and reticuloendothelial systems or to the action of interfering antibodies. It has not yet been established whether or not the protein A‐Sepharose adsorption technique, or the immunosuppressive treatment, contributed in any way to the result. The observations suggest a new approach to the treatment of haemophiliacs with antibodies of the high‐responding type.
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| 2773. |
- Nilsson, Lars, et al.
(författare)
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Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8.
- 2002
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 100:1, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Clonality studies of mature cells suggest that the primary transformation event in myelodysplastic syndrome (MDS) most frequently occurs in a myeloid-restricted progenitor, a hypothesis supported by recent studies of purified CD34(+)Thy1(+) hematopoietic stem cells (HSCs) in cases with trisomy 8 (+8). In contrast, we recently demonstrated that a lymphomyeloid HSC is the target for transformation in MDS cases with del(5q), potentially reflecting heterogeneity within MDS. However, since +8 is known to frequently be a late event in the MDS transformation process, it remained a possibility that CD34(+)CD38(-)Thy1(+) HSC disomic for chromosome 8 might be part of the MDS clone. In the present studies, although a variable fraction of CD34(+)CD38(-)Thy1(+) cells were disomic for chromosome 8, they did not possess normal HSC activity in long-term cultures and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Mixing experiments with normal CD34(+)CD38(-) cells suggested that this HSC deficiency was intrinsic and not mediated by indirect mechanisms. Furthermore, investigation of 4 MDS cases with combined del(5q) and +8 demonstrated that the +8 aberration was always secondary to del(5q). Whereas del(5q) invariably occurs in CD34(+)CD38(-)Thy-1(+) HSCs, the secondary +8 event might frequently arise in progeny of MDS HSCs. Thus, CD34(+)CD38(-)Thy1(+) HSCs are invariably part of the MDS clone also in +8 patients, and little HSC activity can be recovered from the CD34(+) CD38(-)Thy1(+) HSC. Finally, in advanced cases of MDS, the MDS reconstituting activity is exclusively derived from the minor CD34(+)CD38(-) HSC population, demonstrating that MDS stem cells have a similar phenotype as normal HSCs, potentially complicating the development of autologous transplantation for MDS.
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| 2774. |
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| 2775. |
- Nilsson, Lars, et al.
(författare)
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The molecular signature of MDS stem cells supports a stem-cell origin of 5q-myelodysplastic syndromes
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:8, s. 3005-3014
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Tidskriftsartikel (refereegranskat)abstract
- Global gene expression profiling of highly purified 5q-deleted CD34+CD38–Thy1+ cells in 5q– myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38–Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q– stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.
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| 2776. |
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| 2777. |
- Nilsson, R. Jonas A., et al.
(författare)
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Blood platelets contain tumor-derived RNA biomarkers
- 2011
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Ingår i: Blood. - New York : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:13, s. 3680-3683
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Tidskriftsartikel (refereegranskat)abstract
- Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.
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| 2778. |
- Nilsson Sojka, Birgitta, et al.
(författare)
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The blood donation experience : self-reported motives and obstacles for donating blood
- 2008
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Ingår i: Vox Sanguinis. - Oxon : Blackwell Publishing. - 0042-9007 .- 1423-0410. ; 94:1, s. 56-63
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives The aim of the study was to investigate motives for donating blood as well as difficulties and obstacles associated with blood donation as perceived by the donors themselves.Materials and Methods Six hundred consecutive blood donors (i.e. all blood donors with a history of at least one previous whole blood donation attending, during nine working days, the Blood Centre of Umea University Hospital) received a self-administered questionnaire that contained questions aimed at elucidating motives for donating blood (general motives for donating blood, specific motives for the first donation and motives for continuing to be an active blood donor). Questions concerning difficulties and obstacles that had to be overcome in order to continue being a blood donor were also included in the questionnaire.Results Altogether 531 whole blood donors filled in the questionnaire (88.5%; 322 men and 209 women). No statistically significant differences were found between male and female blood donors concerning general reasons and motives related to donating blood. The most frequently reported reasons for giving blood the first time were 'influence from a friend' (47.2% of donors) and 'request via media' (23.5% of donors). Among general reasons/motives with highest ranking of importance, the most commonly reported motive for donating blood were 'general altruism' (40.3%), 'social responsibility/obligation' (19.7%) and 'influence from friends' (17.9%). General altruism' and 'social responsibility/obligation' were also the most frequent reasons for continuing to donate blood (68.4 and 16.0%, respectively). The most commonly reported obstacle to becoming a regular blood donor was 'laziness' (19.1%) followed by 'fear of needles' (10.5%).Conclusions Altruism was the most common general motive for donating blood and also for continuing to be an active blood donor. Yet, for the first blood donation, direct 'influence from friends/relatives', 'media appeal' and other types of recruitment were more commonly reported as reasons or motives for donating blood than altruism. The findings support the notion that different strategies should be used/adopted to get people to donate blood the first time (e.g. recruitment through other blood donors using, for example, the 'bring a friend along' method) and to retain these subjects as active blood donors (e.g. by information and by strengthening their sense of being a blood donor or their self-efficacy etc.).
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| 2779. |
- Nilsson, Therese, et al.
(författare)
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A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 120:6, s. 960-969
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Tidskriftsartikel (refereegranskat)abstract
- The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were + 9, - 13, + 15, + 19, + 11 and - Y. Trisomy 11 and monosomy 16 were more common among men, while -X was more frequent among women. Loss of Y as the sole change and + 5 were more common in elderly patients, and - 14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors.
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| 2780. |
- Nilsson, Therese, et al.
(författare)
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Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation
- 2002
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 68:6, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.
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