| 1. |
- Adolfsson, Jörgen, et al.
(författare)
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Identification of Flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential: A revised road map for adult blood lineage commitment
- 2005
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Ingår i: Cell. - : Elsevier (Cell Press). - 0092-8674 .- 1097-4172. ; 121:2, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.
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| 2. |
- Ahlqvist-Rastad, Jane, et al.
(författare)
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Erythropoietin therapy and cancer related anaemia : updated Swedish recommendations
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:3, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.
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| 3. |
- Ahmad, Faiyaz, et al.
(författare)
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Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the beta(3)-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes
- 2009
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Ingår i: BIOCHEMICAL JOURNAL. - 0264-6021. ; 424:3, s. 399-410
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Tidskriftsartikel (refereegranskat)abstract
- In adipocytes, PDE3B (phosphodiesterase 3B) is an important regulatory effector in signalling pathways controlled by insulin and cAMP-increasing hormones. Stimulation of 3T3-L1 adipocytes with insulin or the beta(3)-adrenergic receptor agonist CL316243 (termed CL) indicated that insulin preferentially phosphorylated/activated PDE3B associated with internal membranes (endoplasmic reticulum/Golgi), whereas CL preferentially phosphorylated/activated PDE3B associated with caveolae. siRNA (small interfering RNA)-mediated KD (knockdown) of CAV-1 (caveolin-1) in 3T3-L1 adipocytes resulted in down-regulation of expression of membrane-associated PDE3B. Insulin-induced activation of PDE3B was reduced, whereas CL-mediated activation was almost totally abolished. Similar results were obtained in adipocytes from Cav-1-deficient mice. siRNA-mediated KID of CAV-1 in 3T3-L1 adipocytes also resulted in inhibition of CL-stimulated phosphorylation of HSL (hormone-sensitive lipase) and perilipin A, and of lipolysis. Superose 6 gel-filtration chromatography of solubilized membrane proteins from adipocytes stimulated with insulin or CL demonstrated the reversible assembly of distinct macromolecular complexes that contained P-32-phosphorylated PDE3B and signalling molecules thought to be involved in its activation. Insulin- and CL-induced macromolecular complexes were enriched in cholesterol, and contained certain common signalling proteins [14-3-3, PP2A (protein phosphatase 2A) and cav-1]. The complexes present in insulin-stimulated cells contained tyrosine-phosphorylated IRS-1 (insulin receptor substrate 1) and its downstream signalling proteins, whereas CL-activated complexes contained beta(3)-adrenergic receptor, PKA-RII [PKA (cAMP-dependent protein kinase)-regulatory subunit] and HSL. Insulin- and CL-mediated macromolecular complex formation was significantly inhibited by CAV-1 KID. These results suggest that cav-1 acts as a molecular chaperone or scaffolding molecule in cholesterol-rich lipid rafts that may be necessary for the proper stabilization and activation of PDE3B in response to CL and insulin.
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| 4. |
- Akerblad, P, et al.
(författare)
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Gene expression analysis suggests that EBF-1 and PPAR gamma 2 induce adipogenesis of NIH-3T3 cells with similar efficiency and kinetics
- 2005
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 23:2, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of multipotent mesenchymal stem cells into lipid-accumulating adipocytes is a physiological process induced by transcription factors in combination with hormonal stimulation. We have used Affymetrix microarrays to compare the adipogenic differentiation pathways of NIH-3T3 fibroblasts induced to undergo in vitro differentiation by ectopic expression of early B cell factor (EBF)-1 or peroxisome proliferator-activated receptor (PPAR)gamma 2. These experiments revealed that commitment to the adipogenic pathway in the NIH-3T3 cells was not reflected in gene expression until 4 days after induction of differentiation. Furthermore, gene expression patterns at the earlier time points after stimulation indicated that EBF-1 and PPAR gamma 2 induced different sets of genes, while the similarities increased upon differentiation, and that several genes linked to adipocyte differentiation were also transiently induced in the vector-transduced cells. These data suggest that the initial activation of genes associated with adipocyte development is independent of commitment to the adipogenic pathway and that EBF-1 and PPAR gamma 2 induce adipocyte differentiation with comparable kinetics and efficiency.
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| 5. |
- Albertsson, Maria, et al.
(författare)
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Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
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| 6. |
- Albin, Bjorn, et al.
(författare)
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Higher mortality and different pattern of causes of death among foreign-born compared to native Swedes 1970-1999
- 2006
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Ingår i: Journal of Immigrant and Minority Health. - : Springer Science and Business Media LLC. - 1557-1912 .- 1557-1920. ; 8:2, s. 101-113
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Tidskriftsartikel (refereegranskat)abstract
- In a previous Swedish longitudinal study of mortality among 723,948 foreign born and native-born Swedes, 1970-1999, increased mortality was found among foreign-born persons. This study describes and analyses the differences in mortality between 361,974 foreign-born persons and 361,974 native Swedes during the period 1970-1999, based on data from Statistics Sweden and the National Board of Health and Welfare. The mortality pattern showed dissimilarities; with a significantly higher number of deaths among foreign-born persons in six diagnose groups and a significantly lower mean age at time of death. A high number of deaths were found for migrants from Denmark in Neoplasm, for migrants from Finland and Poland in Diseases of the circulatory system and for migrants from Yugoslavia in Symptoms, signs and ill-defined conditions. There is a tendency to a more similar pattern between foreign- and Swedish-born persons over time. Migration may be a risk factor for health, and therefore seems to be an important factor to consider when studying morbidity and health and when planning preventive work.
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| 7. |
- Albin, B, et al.
(författare)
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Mortality among 723 948 foreign- and native-born Swedes 1970-1999
- 2005
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Ingår i: European Journal of Public Health. - Oxford, UK : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 15:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mortality in a population is regarded as an accurate and valid measure of the population's health. There are a few international studies, predominantly cross- sectional, of mortality among all foreign- born compared with an indigenous population, and the results have varied. No Swedish longitudinal study describing and analysing mortality data was found in a literature review. Methods: This study describes and analyses the differences in mortality between foreign- born persons and native Swedes during the period 1970 - 1999, based on data from Statistics Sweden and the National Board of Health and Welfare. The database consisted of 723 948 persons, 361 974 foreign- born living in Sweden in 1970, aged >= 16 years, and 361 974 Swedish controls matched for age, sex, occupation and type of employment, living in the same county in 1970. Results: The results showed increased mortality for foreign- born persons compared with the Swedish controls [ odds ratio ( OR) 1.08; 95% confidence interval ( CI) 1.07 - 1.08]. Persons who had migrated ` late' ( 1941 - 1970) to Sweden were 2.5 years younger at time of death than controls. In relation to country of birth, the highest risk odds were for men born in Finland ( OR 1.21), Denmark ( OR 1.11) and Norway/ Iceland ( OR 1.074). Age cohorts of foreign- born persons born between 1901 and 1920 had higher mortality at age 55 - 69 years than cohorts born between 1921 and 1944. Conclusions: Migrants had higher mortality than the native population, and migration may be a risk factor for health; therefore, this seems to be an important factor to consider when studying mortality and health.
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| 8. |
- Alkan Olsson, Johanna, et al.
(författare)
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Local stakeholders acceptance of model-generated data used as a communication tool in water management: The Ronnea study
- 2005
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Ingår i: Ambio. - : Royal Swedish Academy of Sciences. - 0044-7447 .- 1654-7209. ; 34:7, s. 507-512
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to increase the knowledge of local stakeholders acceptance of model-generated data when used as a communication tool in water quality management. The Ronnea catchment in the southwest of Sweden was chosen as the study area. The results indicate the model-generated data served as a uniting factor. Simultaneously, the stakeholders were concerned with presented data, the main problems being sources of pollution, which were not accounted for, lack of trustworthiness when measuring pollution, and the uncertainty of the impact of natural variation and delayed effects. Four clusters of factors were identified as influencing stakeholders acceptance of the model-generated data: confidence in its practical applications, confidence in the people involved in or providing material for the dialog (such as experts, decision-makers, and media), the social characteristics of the participants (such as age and profession), and the way of communicating the data (such as tone of communication, group composition, duration, and geographical scope of the dialog). The perception of the fairness of the practical application of given model-generated data was also an important factor for acceptance.
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| 9. |
- Alkner, Sara, et al.
(författare)
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Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women : Results from a controlled randomised trial
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:14, s. 2496-2502
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial. Patients and methods: Premenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years. Results: In the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients less than40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40-49 years of age or ≥50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time. Conclusion: In this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women less than40 years of age. The effect of tamoxifen was not significantly dependent on time.
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| 10. |
- Almer, Sven, et al.
(författare)
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6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients
- 2009
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 41:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.
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