| 1. |
- Englund, Hillevi, 1980-, et al.
(författare)
-
Oligomerization partially explains the lowering of Aβ42 in Alzheimer's disease cerebrospinal fluid
- 2009
-
Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 6:4, s. 139-147
-
Tidskriftsartikel (refereegranskat)abstract
- Background/aim: The lowering of natively analyzed Aβ42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer’s disease (AD). Presence of Aβ oligomers can interfere with such analyses causing underestimation of Aβ levels due to epitope masking. The aim was to investigate if the lowering of CSF Aβ42 seen is caused by oligomerization. Methods: Aβ42 was analyzed under both denaturing and non-denaturing conditions. An Aβ42 oligomer ratio was calculated from these quantifications. Presence of oligomers leads to Aβ42 epitope masking during non-denaturing assays, resulting in a higher ratio. Results: The Aβ42 oligomer ratio was used for assessment of oligomerized Aβ in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured Aβ42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Aβ42 oligomer ratio in CSF. Conclusion: Combining denaturing and non-denaturing quantifications of Aβ42 into an oligomer ratio enables assessment of Aβ oligomers in biological samples. The increased Aβ42 oligomer ratio for AD and MCI indicates presence of oligomers in CSF and that the lowering of natively measured Aβ42 is caused by oligomerization.
|
|
| 2. |
- Giedraitis, Vilmantas, et al.
(författare)
-
New Alzheimer's disease locus on chromosome 8
- 2006
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 43:12, s. 931-935
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Family history is one of the most consistent risk factors for dementia. Therefore, analysis of families with a distinct inheritance pattern of disease can be a powerful approach for the identification of previously unknown disease genes. Objective: To map susceptibility regions for Alzheimer's disease. Methods: A complete genome scan with 369 microsatellite markers was carried out in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least one member with age at onset of <= 65 years. Mutations in known early-onset Alzheimer's disease susceptibility genes have been excluded. All people were genotyped for APOE, but no clear linkage with the epsilon 4 allele was observed. Results: Although no common disease locus could be found in all families, in two families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, a non-parametric multi-marker logarithm of the odds (LOD) score of 4.2 (p = 0.004) was obtained and analysis based on a dominant model showed a parametric LOD score of 2.4 for this region. All six affected members of this family shared a haplotype of 10 markers spanning about 40 cM. Three affected members in another family also shared a haplotype in the same region. Conclusion: On the basis of our data, we propose the existence of a dominantly acting Alzheimer's disease susceptibility locus on chromosome 8.
|
|
| 3. |
|
|
| 4. |
- Johansen, Kari, et al.
(författare)
-
Norovirus strains belonging to the GII.4 genotype dominate as a cause of nosocomial outbreaks of viral gastroenteritis in Sweden 1997-2005 - Arrival of new variants is associated with large nation-wide epidemics
- 2008
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 42:2, s. 129-134
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In recent years an increase of the incidence of nosocomial outbreaks caused by noroviruses has been observed throughout Sweden, with high peaks noted in the winter seasons 2002/2003 and 2004/2005, respectively. Objectives: To phylogenetically characterize norovirus strains causing nosocomial outbreaks from 1997 to 2005 and estimate the impact of norovirus-like disease on the Swedish health care system during the peak season 2002/2003 when a new variant of norovirus occurred. Study design: Stool samples from 115 randomly selected nosocomial outbreaks occurring during 1997-2005 throughout Sweden were studied by RT-PCR and sequencing. In addition, to investigate the impact on the health-care system, a questionnaire was distributed to infection control units (n = 90) serving all Swedish hospitals, nursing homes and other health-care institutions during the largest epidemic of nosocomial outbreaks. Results: Sequencing of 279 nucleotides of the norovirus RNA polymerase gene in stools containing norovirus RNA showed that strains belonging to the GII.4 genotype dominated. Each of the two large epidemics was due to a new variant within this cluster. The questionnaire revealed that 30,000-35,000 episodes of nosocomial norovirus-like infections occurred in 80 of 82 major Swedish hospitals affected in 2002/2003. Conclusion: New norovirus variants within the cluster GGII.4 may have a major impact on the health-care system. (c) 2008 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Jønler, Morten, et al.
(författare)
-
Quality of life in patients with skeletal metastases of prostate cancer and status prior to start of endocrine therapy : results from the Scandinavian Prostate Cancer Group Study 5.
- 2005
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 39:1, s. 42-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Prostate cancer (PC) is a highly lethal neoplastic disease affecting the physical, mental and social well-being of patients, i.e. their quality of life (QOL). Patients suffering from metastatic PC are faced with serious decisions regarding treatment strategies. Therefore, QOL information has become a crucial element of decision making in this group of patients. The first objective of this study was to describe QOL in a group of patients diagnosed with metastatic PC and skeletal metastases. At the time of evaluation the patients had not received any treatment but were evaluated before entering a study of androgen-modulating therapy (the Scandinavian Prostate Cancer Group study 5). The second objective was to identify demographic and disease-related factors affecting QOL. MATERIAL AND METHODS: A total of 917 patients with metastatic PC were evaluated using a well-described and validated questionnaire [European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (EORTC QLQ-C30)]. The characteristics of the PC were noted, and simultaneously patients were evaluated with respect to use of analgesics, pain and performance status using a scoring system. Biochemical tests were performed when patients entered the study. A multivariate regression analysis was performed to analyse the correlations between QOL scores, patient demographics and disease-related data. RESULTS: The patients reported QOL scores significantly lower than those in the background population. Pain and fatigue were pronounced, whereas dyspnoea, insomnia, loss of appetite, constipation and diarrhoea were less prominent. Patients with high tumour grades, high PSPA scores (the sum of the pain score, the performance status and the use of analgesics) and those using analgesics had significantly lower QOL scores than the other patients. CONCLUSIONS: Patients with metastatic PC have reduced QOL. Our findings are in line with those of other studies of QOL among patients with this disease as evaluated by means of the EORTC QLQ-C30 questionnaire. Baseline data from studies like this provide important information when treatment modalities for PC are evaluated.
|
|
| 6. |
- Lång, Lars-Ove, et al.
(författare)
-
Digital insamling av vattentäktsdata till databas DGV– exempel på metodik för miljömålsuppföljning
- 2007
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SGU har under några år arbetat med att bygga upp ett system för överföring av vattentäktsdatafrån landets kommuner till en nationell databas för grundvattenförekomster och vattentäkter(DGV). Arbetet har främst varit inriktat mot landets allmänna vattentäkter, men även övrigavattentäkter som försörjer > 50 personer eller har ett uttag > 10m3/dygn ingår. Ett av huvudskälentill uppbyggnaden av databasen är behovet inom miljömålsarbetet av data avseende vattenförsörjningen.Användningen ligger framförallt inom miljömålet ”Grundvatten av god kvalitet”,men uppgifter i DGV har även tillämpning inom andra miljömål. Detta projekt är en del iarbetet med att utveckla DGV samt beskriva användbarheten utifrån miljömålssynpunkt.Arbetet med insamling av vattentäktsuppgifter direkt från kommunerna inleddes i slutet av2002. Under 2006 har för första gången en förfrågan om uppdatering av inlagrade uppgifterskett. I januari 2007 var 215 kommuner färdiga med inregistreringen av allmänna vattentäkter.Inlämningen av uppgifter från kommunerna är frivillig. Därför har inför efterfrågan av dataavstämning skett mot ett antal utvalda kontaktkommuner så att uppgiftslämnandet innebär enrimlig arbetsinsats. Det har också eftersträvats från SGUs sida att ha en effektiv teknisk supportoch kommunens egna data är alltid tillgängliga via webben. För att underlätta för kommunernainsamlas vattenanalysresultat direkt från anlitade laboratorier efter att avtal undertecknats avkommunerna eller vattentäktsinnehavare.I denna rapport ingår en sammanfattning av hur insamlingen av vattentäktsdata till DGV gårtill samt kortfattade beskrivningar av uppbyggnaden av databas och webbapplikation. För meruppgifter om den tekniska utformningen kan kontakt tas med SGU.En sammanfattning ingår också i rapporten avseende användningen av DGV-data imiljömålsarbetet på nationell, regional och lokal nivå. Uppgifter från DGV används vid framtagandeav indikatorer samt vid uppföljningen av dessa. DGV-data är ett av de viktigasteunderlagen i det nu pågående arbetet med den andra Fördjupade utvärderingen av miljömålet”Grundvatten av god kvalitet”.Arbetet med DGV är omfattande vad gäller kontakter och systemuppbyggnad. Ett stort antalpersoner har medverkat vid inmatningen av uppgifter hos kommunerna. Deras intresse ochengagemang har inneburit att de flesta av landets allmänna vattentäkter nu har registrerats iDGV. Arbetet med DGV innebär ett stort erfarenhetsutbyte mellan SGU, kommunerna ochandra berörda myndigheter. Förhoppningen är att verksamheten inom DGV ökar förståelsen församverkan mellan kommunerna och statliga myndigheter inom miljömålsarbetet. Denerfarenhet av webbaserad insamling av data som DGV-arbetet innebär bör kunna användas isamband med annat miljömålsarbete.
|
|
| 7. |
- Wollmer, M Axel., et al.
(författare)
-
Association study of cholesterol-related genes in Alzheimer's disease
- 2007
-
Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 8:3, s. 179-188
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.
|
|
| 8. |
- Xue, Yuan, et al.
(författare)
-
FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
- 2008
-
Ingår i: Proceedings of The National Academy of Sciences of The United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:29, s. 10167-10172
-
Tidskriftsartikel (refereegranskat)abstract
- Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.
|
|
