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Sökning: LAR1:lu > (2005-2009) > Tidskriftsartikel > Engelska > Linköpings universitet

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  • Adolfsson, J, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 - Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Taylor & Francis Group. - 0036-5599. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising > 97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <= 6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged >= 75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
  • Ahmad, Faiyaz, et al. (författare)
  • 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
  • Ingår i: BIOCHEMICAL JOURNAL. - 0264-6021. ; 424:3, s. 399-410
  • 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.
  • Akesson, K., et al. (författare)
  • The non-inherited maternal HLA haplotype affects the risk for type 1 diabetes
  • 2009
  • Ingår i: International journal of immunogenetics. - 1744-3121. ; 36:1, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to test the hypothesis that the human leucocyte antigen (HLA) haplotype that is not inherited from the mother, that is, the non-inherited maternal antigen (NIMA) affects the risk for type 1 diabetes (T1D). A total of 563 children with T1D and 286 non-diabetic control children from Sweden were genotyped for DRB1, DQA1 and DQB1 alleles. The frequency of positively (DR4-DQA1*0301-B1*0302 and DR3-DQA1*0501-B1*0201), negatively (DR15-DQ A1*0102-B1*0602) or neutrally (all other) T1D associated HLA haplotypes were compared between NIMA and non-inherited paternal antigen (NIPA). All comparisons were carried out between HLA-matched patients and controls. The frequency of positively associated NIMA was higher among both DR4/X-positive healthy individuals compared wit DR4/X-positive patients (P < 0.00003) and DR3/X-positive healthy individuals compared with DR3/X-positive patients (P < 0.009). No such difference was observed for NIPA. High-risk NIMA was increased compared to NIPA among healthy DR3/X- and DR4/X-positive children (P < 0.05). There was no difference in frequency of positively associated haplotypes between patient NIMA and NIPA. The NIMA but not the NIPA affects the risk for T1D, suggesting that not only the inherited but also non-inherited maternal HLA haplotypes, perhaps through microchimerism or other mechanisms, may influence the risk for the disease.
  • Alkan Olsson, Johanna, et al. (författare)
  • Local stakeholders acceptance of model-generated data used as a communication tool in water management: : The Ronnea study
  • 2005
  • Ingår i: Ambio. - 0044-7447. ; 34:7, s. 507-512
  • 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.
  • Alkner, S., et al. (författare)
  • Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: Results from a controlled randomised trial.
  • 2009
  • Ingår i: European journal of cancer (Oxford, England : 1990). - 1879-0852. ; 45, s. 2496-2502
  • 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 <40 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 <40 years of age. The effect of tamoxifen was not significantly dependent on time.
  • Almer, S. H. C., et al. (författare)
  • 6-Thioguanine therapy in Crohn's disease-Observational data in Swedish patients
  • 2009
  • Ingår i: Digestive And Liver Disease. - Pacini Editore. - 1590-8658. ; 41:3, s. 194-200
  • 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 Crohn's 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. (C) 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
  • Amundin, Mats, 1947-, et al. (författare)
  • An echolocation visualization and interface system for dolphin research
  • 2008
  • Ingår i: Journal of Acoustical Society of America. - 0001-4966. ; 123:2, s. 1188-1194
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study describes the development and testing of a tool for dolphin research. This tool was able to visualize the dolphin echolocation signals as well as function as an acoustically operated "touch screen." The system consisted of a matrix of hydrophones attached to a semitransparent screen, which was lowered in front of an underwater acrylic panel in a dolphin pool. When a dolphin aimed its sonar beam at the screen, the hydrophones measured the received sound pressure levels. These hydrophone signals were then transferred to a computer where they were translated into a video image that corresponds to the dynamic sound pressure variations in the sonar beam and the location of the beam axis. There was a continuous projection of the image back onto the hydrophone matrix screen, giving the dolphin an immediate visual feedback to its sonar output. The system offers a whole new experimental methodology in dolphin research and since it is software-based, many different kinds of scientific questions can be addressed. The results were promising and motivate further development of the system and studies of sonar and cognitive abilities of dolphins. © 2008 Acoustical Society of America.
  • Anderson, Kristina, et al. (författare)
  • Ectopic expression of PAX5 promotes self renewal of bi-phenotypic myeloid progenitors co-expressing myeloid and B-cell lineage associated genes.
  • 2007
  • Ingår i: Blood. - American Society of Hematology. - 0006-4971. ; 109:Jan 11, s. 3697-3705
  • Tidskriftsartikel (refereegranskat)abstract
    • The transcription factor PAX5 is a critical regulator of B-cell commitment and development. Although normally not expressed in myeloid progenitors, PAX5 has recently been shown to be frequently expressed in myeloid malignancies and to suppress expression of myeloid differentiation genes, compatible with an effect on the differentiation or maintenance of myeloid progenitors. However, previous studies in which PAX5 was ectopically expressed in normal myeloid progenitors in vivo and in vitro provided conflicting results as to the effect of PAX5 on myeloid development. Herein, we demonstrate that on ectopic expression of PAX5 in bone marrow multipotent stem/progenitor cells, cells with a biphenotypic B220+GR-1/MAC-1+ phenotype are produced. These remain cytokine-dependent, but unlike control-transduced cells they sustain long-term generation of myeloid progenitors in vitro and remain capable of myeloid differentiation. Notably, PAX5+B220+GR-1/MAC-1+ myeloid progenitors coexpress, at the single-cell level, myeloid genes and otherwise B-cell–specific PAX5 target genes. These findings establish that ectopic expression of PAX5 introduces extensive self-renewal properties in otherwise short-lived myeloid progenitors. Along with the established ectopic expression of PAX5 in acute myeloid leukemia, this motivates a careful investigation of the potential involvement of ectopic PAX5 expression in myeloid and biphenotypic leukemias.
  • Andersson, Anna, et al. (författare)
  • FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns.
  • 2008
  • Ingår i: Genes Chromosomes Cancer. - 1045-2257. ; 47, s. 64-70
  • Tidskriftsartikel (refereegranskat)abstract
    • During 1995-2004, 209 children/adolescents were diagnosed with acute lymphoblastic or myeloid leukemia (ALL, AML) in Southern Sweden, of which 177 (85%), comprising 128 B-lineage ALL, 34 AML, and 15 T-cell ALL, could be analyzed for internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD, mutually exclusive) were detected. None of the T-cell ALL harbored any mutations. ITD and ATKD were found in 2% and 6% of the B-lineage ALL and in 12% and 9% of the AML, being particularly common in high hyperdiploid ALL (14%), ALL (20%), and AML (23%) with 11q23/MLL rearrangements, and in AML with a normal karyotype (60%). All ATKD-positive AML with MLL rearrangements harbored the t(9,11)(p21,q23). Global gene expression data were available for 76 of the B-lineage ALL and 19 of the AML, of which 6 (8%) and 3 (16%) had FLT3 mutations, respectively. No distinct expression pattern associated with FLT3 mutations was identified. © 2007 Wiley-Liss, Inc.
  • Andersson, A., et al. (författare)
  • Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
  • 2007
  • Ingår i: Leukemia. - Nature Publishing Group. - 0887-6924. ; 21:6, s. 1198-1203
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
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