| 2751. |
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| 2752. |
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| 2753. |
- Lindholm, C., et al.
(författare)
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Failure to reach hematopoietic allogenic stem cell transplantation in patients with myelodysplastic syndromes planned for transplantation : a population-based study
- 2022
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 57, s. 598-606
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Tidskriftsartikel (refereegranskat)abstract
- The only potential cure for patients with myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HCT). However, a proportion of patients who are HCT candidates do not finally get transplanted. This population-based study aimed to characterize HCT candidates were attempting to reach HCT fail and to identify causes and risk factors for failure. Data were collected from (1) the national Swedish registry, enrolling 291 transplant candidates between 2009-2018, and (2) Karolinska University Hospital, enrolling 131 transplantation candidates between 2000 and 2018. Twenty-five % (nation-wide) and 22% (Karolinska) failed to reach HCT. Reasons for failure to reach HCT were progressive and refractory disease (47%), no donor identified (22%), identification of comorbidity (18%), and infectious complications (14%). Factors associated with failure to reach HCT were IPSS-R cytogenetic risk-group very poor, mixed MDS/MPN disease, low blast count (0-4.9%), and low hemoglobin levels (<= 7.9 g/dL). Transplanted patients had a longer overall survival (OS) compared to patients who failed to reach transplantation (83 months versus 14 months; p < 0.001). The survival advantage was seen for the IPSS-R risk groups intermediate, high, and very high. This study demonstrated that a high proportion of HCT-candidates fail to reach HCT and underlines the difficulties associated with bridging MDS patients to HCT.
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| 2754. |
- Lindmark, Anders
(författare)
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On the Biosynthesis and Processing of Cathepsin G, Leukocyte Elastase, and Azurocidin neutrophil granule members of a hematopoietic serine protease superfamily
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The serine proteases cathepsin G, leukocyte elastase, proteinase 3, and the inactive protease homologue azurocidin, stored in the azurophil granules of neutrophils, belong to a hematopoietic serine protease superfamily with members in mature effector cells of bone marrow origin. Promonocytic U-937 cells were used for studying the biosynthesis of cathepsin G and leukocyte elastase by biosynthetic radiolabelling. The proteases were found to be synthesized as precursor forms that were subjected to processing, including acquisition of N-linked complex oligosaccharides. Targeting to a granule compartment was also demonstrated. Using brefeldin A, monensin, and ammonium chloride, the subcellular localization of distinct processing events was characterized. To make possible an evaluation of the importance of distinct protein motifs, a transfectable cellular model for studying the processing was established. cDNA encoding human cathepsin G was transfected to the rat RBL cell line, after which the model was proven valid by characterizing the activation, processing, and sorting of cathepsin G. Mutant cDNAs encoding cathepsin G and leukocyte elastase lacking carboxyl-terminal peptide extensions, normally removed during processing, were transfected to RBL cells. The mutant proteins were found to be activated and sorted to granules, approximately as efficiently as the wild type proteins, hence ruling out a critical role of the propeptides for folding, stability or molecular targeting. The granule thiol protease dipeptidyl peptidase I (DPP I) has been suggested as responsible for the activation of all hematopoietic serine proteases. It was, however, not possible to activate procathepsin G, expressed in COS-7 cells, neither by co-transfection of rat DPP I cDNA nor by in vitro incubation with purified bovine DPP I. After transfection to RBL cells, a novel amino-terminal processing pattern distinct from that of other granule serine proteases was demonstrated for the synthesis and processing of azurocidin.
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| 2755. |
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| 2756. |
- Lindqvist, Camilla A, et al.
(författare)
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T Regulatory Cells in B-Cell Malignancy : Tumor Support or Kiss of Death?
- 2012
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 135:4, s. 255-260
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Forskningsöversikt (refereegranskat)abstract
- It is well established that T regulatory cells (Tregs) counteract tumor immunity. However, conflicting results describing the role of Tregs in hematological tumors warrant further investigations to clarify the interactions between Tregs and the tumor. B-cell malignancy derives from different stages of B-cell development and differentiation in which T-cells play a profound role. The transformed B-cell may still be in need of T-cell help to thrive but simultaneously they may be recognized and destroyed by cytotoxic lymphocytes. Recent reports demonstrate that Tregs can suppress and even kill B-cells as part of their normal function to rescue the body from autoimmunity. An emerging body of evidence points out that Tregs inhibit tumor-specific T-cells but may also have a role in suppressing the progression of the B-cell tumor. In this review, we discuss the origin and function of Tregs and their role in patients with B-cell tumors.
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| 2757. |
- Lindqvist, Pelle, et al.
(författare)
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The relationship between lifestyle factors and venous thromboembolism among women: a report from the MISS study.
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 144, s. 234-240
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Tidskriftsartikel (refereegranskat)abstract
- There has been a great advance in our knowledge of the role that thrombophilic factors play in the risk of venous thromboembolic events (VTE). However, the effect of lifestyle factors on VTE has been inadequately explored in large scale studies of women. This cohort study comprised one thousand native Swedish women for each age year between 25 and 64 inclusive (total = 40 000) drawn from the South Swedish population registry for 1990 (n = 40 000), who were followed for a mean of eleven years. Seventy-four percent completed a questionnaire at the inception of the study (n = 29 518) and 24 098 women responded to a follow-up inquiry between the years 2000-2002. The main outcome was the relationship between VTE and physical exercise, smoking habits, and alcohol consumption. Moderate drinkers of alcohol (10-15 g/d) and women engaged in strenuous exercise were at half the risk of VTE compared to those who consumed little or no alcohol or lived a sedentary life. Heavy smoking was associated with a 30% increased risk of VTE. Lifestyle factors have a major impact on the risk of VTE. Women non-smokers who were physically active and who consumed alcohol in moderation were at a lower risk of VTE.
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| 2758. |
- Lindvall, Karin, et al.
(författare)
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Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia
- 2006
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 12:1, s. 47-51
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that teenagers with chronic diseases have problems complying with their treatment. The aim of this study was to evaluate the patient's knowledge of haemophilia and his compliance to prophylactic treatment, and the age at which the patient took over the responsibility for his disease and to create educational material for teenagers and adolescents. This was a prospective multicentre study performed in Hemophilia Treatment Centres in Scandinavia. A total of 108 of 134 patients, between 13 and 25 years completed the questionnaire, a response rate of 80%. Eighty-three patients had a severe form of haemophilia, 24 patients in moderate form and one patient did not know the severity of his disease. Seventy-eight patients were on prophylactic treatment. The median age for starting prophylactic treatment was 3.0 years and the median age for the patient performing venepuncture was 11.6 years. Sixty-seven of 78 patients knew that the best time to give prophylactic treatment was in the morning. Even though the patients were on prophylactic treatment, 47 of 78 patients took additional treatment before sports activities. At a mean age of 14.1 years the patient himself had the responsibility for his disease and treatment. In the cohort of 108 patients, 73 were aware of their haemophilia heredity. This study shows a rather high degree of knowledge of haemophilia and compliance with treatment among the patients but it is of great importance for the nurse to continuously improve the patient's compliance and keep him aware of the benefit of regular treatment for his future well being.
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| 2759. |
- Lindvall, Karin, et al.
(författare)
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Daily dosing prophylaxis for haemophilia : A randomized crossover pilot study evaluating feasibility and efficacy
- 2012
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 18:6, s. 855-859
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Tidskriftsartikel (refereegranskat)abstract
- Regular replacement therapy (prophylaxis) for haemophilia has been shown to prevent development of disabling arthropathy and to provide a better quality of life compared to treatment on demand; however, at a substantially higher cost. Calculations based on pharmacokinetic principles have shown that shortening dose intervals may reduce cost. The aim of this prospective, randomized, crossover pilot study was to address whether daily dosing is feasible, if it reduces concentrate consumption and is as effective in preventing bleeding as the standard prophylactic dosing regimen. In a 12 + 12 month crossover study, 13 patients were randomized to start either their own previously prescribed standard dose, or daily dosing adjusted to maintain at least the same trough levels as obtained with the standard dose. Ten patients completed the study. A 30% reduction in cost of factor concentrates was achieved with daily prophylaxis. However, the number of bleeding events increased in some patients in the daily dosing arm and patients reported decreased quality of life during daily prophylaxis. Daily treatment had a greater impact on daily life, and the patients found it more stressful.Prophylaxis with daily dosing may be feasible and efficacious in some patients. A substantial reduction of factor consumption and costs can be realized, but larger studies are needed before the introduction of daily prophylaxis into clinical routine can be recommended.
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| 2760. |
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