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- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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- Banka, Vinay, et al.
(författare)
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Development of brain-penetrable antibody radioligands for in vivo PET imaging of amyloid-β and tau
- 2023
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Ingår i: Frontiers in nuclear medicine. - : Frontiers Media S.A.. - 2673-8880. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aβ) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood-brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aβ aggregates via ex vivo imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled specifically engineered bispecific antibody probes for the selective detection of tau and Aβ aggregates to evaluate their feasibility and specificity, particularly for in vivo PET imaging.METHODS: We first created and evaluated (via both in vitro and ex vivo studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aβ or tau or with their respective scFv. Using [18F]SFB as the prosthetic group, all four 18F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [18F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ~ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size exclusion gravity column.RESULTS: Based on both in vitro and ex vivo evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [18F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [18F]SFB and bispecific antibodies showed a 65%-83% conversion efficiency with radiochemical purities of 95%-99% by radio-TLC.CONCLUSIONS: We successfully labeled four novel and specifically engineered bispecific antibodies with [18F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aβ aggregates in the brain of transgenic AD mice via in vivo PET imaging.
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- Steingrimsson, Einar, 1955, et al.
(författare)
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A total population-based cohort study of female psychiatric inpatients who have served a prison sentence
- 2015
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Ingår i: Criminal Behaviour and Mental Health. - : Wiley. - 0957-9664. ; 25:3, s. 220-225
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStudies of the overlap between severe mental disorder and criminality tend to focus on prison populations rather than psychiatric populations. AimsOur aims were to establish the prevalence of previous imprisonment among female psychiatric inpatients and test relationships between diagnoses, mortality and imprisonment. MethodsA nationwide cohort of 18-65-year-old women who had been hospitalised for psychiatric disorder between January 1983 and March 2008 was identified from a hospital records database and linked to the database of the Prison and Probation Administration of Iceland as well as the National Register of causes of death at Statistics Iceland from January 1985. ResultsSix thousand and ninety-four women had had at least one psychiatric hospitalisation, 102 of them had been imprisoned on 172 occasions between them, giving an imprisonment rate of 118 per 100,000 over the 24year period of study. The crude imprisonment proportion was 1.7% during a 20-year follow-up period; it was at its peak (5%) among 18-30 year-olds at index admission. Substance use and personality disorders were the most common diagnoses associated with imprisonment. Mortality rates were not statistically different between those imprisoned and not (hazard ratio=1.3, 95% confidence interval 0.5-3.5). Conclusion and implications for practiceWomen admitted to a psychiatric hospital have higher rates of imprisonment than the general population. Because admission predated imprisonment in most cases, this may be seen as an opportunity for early intervention to reduce later criminality. Copyright (c) 2015 John Wiley & Sons, Ltd.
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