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| 2. |
- Bergman, Annika, et al.
(författare)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 3. |
- Biswas, Priti, et al.
(författare)
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Dynamics of Health Care Seeking Behaviourof Elderly People in Rural Bangladesh
- 2006
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Ingår i: International Journal of Ageing and Later Life. - 1652-8670. ; 1:1, s. 69-89
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Tidskriftsartikel (refereegranskat)abstract
- Bangladesh is projected to experience a doubling of its elderly populationfrom the current level of 7 million to 14 million by the end of the nextdecade. Drawing upon qualitative evidence from rural Bangladesh, thisarticle focuses on coping strategies in cases of illness of elderly peopleand the contributing factors in determining the health-seeking behaviourof elderly persons. The sample for this study consisted of elderly menand women aged 60 years or older and their caregivers. Nine focus groupdiscussions and 30 in-depth interviews were conducted. Findingsindicate that old age and ill-health are perceived to be inseparableentities. Seeking health care from a formally qualified doctor is avoideddue to high costs. Familiarity and accessibility of health care providersplay important roles in health-seeking behaviour of elderly persons.Flexibility of health care providers in receiving payment is a crucialdeciding factor of whether or not to seek treatment, and even the type oftreatment sought.
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| 4. |
- Boström, Pontus, 1982, et al.
(författare)
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SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
- 2007
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 9:11, s. 1286-93
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
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| 6. |
- McFarland, Melinda A, et al.
(författare)
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Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation, electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS/MS
- 2005
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Ingår i: J Am Soc Mass Spectrom. - : American Chemical Society (ACS). - 1044-0305. ; 16:5, s. 752-62
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Tidskriftsartikel (refereegranskat)abstract
- Gangliosides play important biological roles and structural characterization of both the carbohydrate and the lipid moieties is important. The FT-ICR MS/MS techniques of electron capture dissociation (ECD), electron detachment dissociation (EDD), and infrared multiphoton dissociation (IRMPD) provide extensive fragmentation of the protonated and deprotonated GM1 ganglioside. ECD provides extensive structural information, including identification of both halves of the ceramide and cleavage of the acetyl moiety of the N-acetylated sugars. IRMPD provides similar glycan fragmentation but no cleavage of the acetyl moiety. Cleavage between the fatty acid and the long-chain base of the ceramide moiety is seen in negative-ion IRMPD but not in positive-ion IRMPD of GM1. Furthermore, this extent of fragmentation requires a range of laser powers, whereas all information is available from a single ECD experiment. However, stepwise fragmentation by IRMPD may be used to map the relative labilities for a series of cleavages. EDD provides the alternative of electron-induced fragmentation for negative ions with extensive fragmentation, but suffers from low efficiency as well as complication of data analysis by frequent loss of hydrogen atoms. We also show that analysis of MS/MS data for glycolipids is greatly simplified by classification of product ion masses to specific regions of the ganglioside based solely on mass defect graphical analysis.
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| 7. |
- Nilsson, Jan, 1963-, et al.
(författare)
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Role and function: Aspects of quality of life of older peoplein rural Bangladesh
- 2005
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Ingår i: Journal of Aging Studies. - : Elsevier BV. - 0890-4065 .- 1879-193X. ; :19, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to explore the meaning of quality of life (QoL) for elderly people in a rural communityin Bangladesh. Data were obtained through in-depth interviews with 11 elderly persons aged 63–86 years.Interview data were analysed using content analysis to determine the conceptual meaning of elderly peoples’experiences of QoL. Two major themes emerged from the data as being of utmost importance in QoL of elderlypeople in rural Bangladesh. These were: (i) having a role in the family and the community and (ii) beingfunctional, both physically and economically. Results also showed that elderly people in rural Bangladeshprioritise being healthy, having a good social network, social support and a secure financial situation in order tohave good QoL. This study is a step towards a better understanding of QoL experienced by the elderly peoplethemselves in a rural Bangladeshi context.
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| 8. |
- Nilsson, Jan, 1963-, et al.
(författare)
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Social Capital and Qualityof Life in Old Age
- 2006
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Ingår i: Journal of Aging and Health. - 0898-2643 .- 1552-6887. ; 18:3, s. 419-434
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this article is to identify determinants of quality of life (QoL) andinvestigate their association with individual- and community-level social capitalamong older people in rural Bangladesh.Across-sectional study of 1,135 elderly persons(aged ≥ 60 years) was conducted in a rural district in Bangladesh. Independentvariables included age, sex, education, economic status of the elderly person, andindividual- and community-level social capital. Self-rated QoL was the dependentvariable. Descriptive analyses were done to showgroup differences in QoL and logisticregression analyses to identify determinants of QoL. Advanced age, poor householdeconomic status, and lowsocial capital at individual and community levels weresignificant determinants of poor QoL among the elderly. This population-based studyprovided empirical evidence that social capital both at individual and community levelswas directly associated with the QoL of elderly people in rural Bangladesh.
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| 9. |
- Nilsson, S., et al.
(författare)
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Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study
- 2007
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Ingår i: Lancet Oncol. - 1470-2045 .- 1474-5488. ; 8:7, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.
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