| 1. |
- Bjarnadottir, M, et al.
(författare)
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Intracellular accumulation of the amyloidogenic L68Q variant of human cystatin C in NIH/3T3 cells
- 1998
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Ingår i: Molecular Pathology. - : BMJ. - 1366-8714. ; 51, s. 317-326
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the cellular transport of L68Q cystatin C, the cystatin variant causing amyloidosis and brain haemorrhage in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA).METHODS: Expression vectors for wild-type and L68Q cystatin C were constructed and used to transfect mouse NIH/3T3 cells. Stable cell clones were isolated after cotransfection with pSV2neo. Clones expressing human wild-type and L68Q cystatin C were compared with respect to secreted cystatin C by enzyme linked immunosorbent assay (ELISA), and for intracellular cystatin C by western blotting and immunofluorescence cytochemistry. Colocalisation studies in cells were performed by double staining with antibodies against human cystatin C and marker proteins for lysosomes, the Golgi apparatus, or the endoplasmic reticulum, and evaluated by confocal microscopy.RESULTS: Concentrations of human cystatin C secreted from transfected NIH/3T3 cells were similar to those secreted from human cells in culture. In general, clones expressing the gene encoding L68Q cystatin C secreted slightly lower amounts of the protein than clones expressing wild-type human cystatin C. Both immunofluorescence cytochemistry and western blotting experiments showed an increased accumulation of cystatin C in cells expressing the gene encoding L68Q cystatin C compared with cells expressing the gene for the wild-type protein. The intracellularly accumulating L68Q cystatin C was insoluble and located mainly in the endoplasmic reticulum.CONCLUSIONS: The cellular transport of human cystatin C is impeded by the pathogenic amino acid substitution Leu68-->Gln. The resulting intracellular accumulation and increased localised concentration of L68Q cystatin C might be an important event in the molecular pathophysiology of amyloid formation and brain haemorrhage in patients with HCCAA.
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| 2. |
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| 3. |
- Bjarnadottir, G. D., et al.
(författare)
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Intravenous Use of Prescription Psychostimulants; A Comparison of the Pattern and Subjective Experience between Different Methylphenidate Preparations, Amphetamine and Cocaine
- 2016
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Ingår i: European Addiction Research. - : S. Karger AG. - 1022-6877 .- 1421-9891. ; 22:5, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Methylphenidate (MPH) has been the most commonly used intravenous (i.v.) substance in Iceland in recent years. In Iceland, MPH is available in 3 forms: immediate-release (IR) tablets (MPH IR, short-acting), sustainable-release (SR) capsules (MPH SR, long-acting) and osmotic-release (OROS) tablets (MPH OROS, long-acting). The aims of the study were to compare the pattern and subjective effects of i.v. MPH use to other i.v. psychostimulants and examine whether the pattern of use differs among MPH preparations. Methods: This is a nationwide descriptive study. Information was collected from 95 i.v. substance users undergoing inpatient detoxification and reporting i.v. MPH use in the last 30 days using a semi-structured interview. Results: MPH SR was both the most commonly used (96%) and preferred i.v. psychostimulant (57%). The intensity and duration of 'euphoria' did not differ between cocaine and MPH SR. No participant reported MPH OROS as their preferred substance even though a third had used it in the past month. Conclusions: The pattern of i.v. MPH use is similar to other psychostimulants among treatment seeking patients. MPH OROS was the least preferred i.v. psychostimulant, despite having the largest market share in Iceland. The results indicate that MPH OROS has less abuse potential than other MPH preparations. (C) 2016 S. Karger AG, Basel
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| 4. |
- Bjarnadottir, G. D., et al.
(författare)
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Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users
- 2017
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Ingår i: Drug and Alcohol Dependence. - : Elsevier BV. - 0376-8716. ; 178, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. Methods: A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. Results: Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (p < 0.0001). The viscosity of the disintegrated MPH was significantly higher for MPH OROS and MPH OCR and the preparation was significantly more time-consuming than for the other MPH samples. No differences were observed between users and non-users. Conclusions: To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations.
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| 5. |
- Bjarnadottir, G. D., et al.
(författare)
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Prevalent intravenous abuse of methylphenidate among treatment-seeking patients with substance abuse disorders: A descriptive population-based study
- 2015
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Ingår i: Journal of Addiction Medicine. - : Lippincott Williams and Wilkins. - 1932-0620. ; 9:3, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Prescription rates of methylphenidate (MPH) are sharply rising in most Western countries. Although it has been reported that MPH has abuse potential, little is known about the prevalence of intravenous (IV) abuse of MPH. The aim of the study was to investigate the prevalence of IV MPH abuse among treatment-seeking IV substance abusers in Iceland. Methods: This is a descriptive population-based study using a semistructured interview assessing sociodemographics, substance abuse history, and the method of administration of 108 IV substance abusers. During 1 year, consecutively admitted adult inpatients with substance use disorder at any detoxification center in Iceland that reported any IV substance abuse in the past 30 days were invited to participate. Abuse was defined as nontherapeutic use of a substance to gain psychological or physiological effect. Results: Prevalence of any IV MPH abuse among participants was 88% in the last 30 days (95% confidence interval [CI], 0.82-0.94) and MPH was the most commonly abused substance (65%) and the preferred substance (63%). Around one third (30%) reportedMPH as the first IV substance ever abused. However, among those reporting a shorter history than 10 years of IV abuse, 42% reported MPH as the first IV substance ever abused. Conclusions: This first nationwide study on IV abuse ofMPH shows that it is common among treatment-seeking IV abusers in Iceland and suggests that MPH has high abuse potential. Therefore, both the use and possible abuse of MPH in those with high abuse potential should be monitored, especially in countries where MPH prescriptions rates are on the rise. Copyright © 2015 American Society of Addiction Medicine.
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| 7. |
- Greenwood, Sarah L., et al.
(författare)
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Exceptions to bed-controlled ice sheet flow and retreat from glaciated continental margins worldwide
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Projections of ice sheet behavior hinge on how ice flow velocity evolves and the extent to which marine-based grounding lines are stable. Ice flow and grounding line retreat are variably governed by the coupling between the ice and underlying terrain. We ask to what degree catchment-scale bed characteristics determine ice flow and retreat, drawing on paleo-ice sheet landform imprints from 99 sites on continental shelves worldwide. We find that topographic setting has broadly steered ice flow and that the bed slope favors particular styles of retreat. However, we find exceptions to accepted rulesof behavior: Regional topographic highs are not always an impediment to fast ice flow, retreat may proceed in a controlled, steady manner on reverse slopes and, unexpectedly, the occurrence of ice streaming is not favored on a particular geological substrate. Furthermore, once grounding line retreat is under way, readvance is rarely observed regardless of regional bed characteristics.
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| 8. |
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| 9. |
- Maller, Ori, et al.
(författare)
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Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression
- 2020
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Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-1122 .- 1476-4660.
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Tidskriftsartikel (refereegranskat)abstract
- Stromal stiffening accompanies malignancy, compromises treatment and promotes tumour aggression. Clarifying the molecular nature and the factors that regulate stromal stiffening in tumours should identify biomarkers to stratify patients for therapy and interventions to improve outcome. We profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with the stiffest stroma. These tissues harbour the highest number of tumour-associated macrophages, whose therapeutic ablation in experimental models reduced metastasis, and decreased collagen crosslinks and stromal stiffening. Epithelial-targeted expression of the crosslinking enzyme, lysyl oxidase, had no impact on collagen crosslinking in PyMT mammary tumours, whereas stromal cell targeting did. Stromal cells in microdissected human tumours expressed the highest level of collagen crosslinking enzymes. Immunohistochemical analysis of biopsies from a cohort of patients with breast cancer revealed that stromal expression of lysyl hydroxylase 2, an enzyme that induces hydroxylysine aldehyde-derived collagen crosslinks and stromal stiffening, correlated significantly with disease specific mortality. The findings link tissue inflammation, stromal cell-mediated collagen crosslinking and stiffening to tumour aggression and identify lysyl hydroxylase 2 as a stromal biomarker.
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| 10. |
- Simkins, Lauren M., et al.
(författare)
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Advances in understanding subglacial meltwater drainage from past ice sheets
- 2022
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Ingår i: Annals of Glaciology. - 0260-3055 .- 1727-5644. ; 63:87-89, s. 83-87
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Tidskriftsartikel (refereegranskat)abstract
- Meltwater drainage beneath ice sheets is a fundamental consideration for understanding ice–bed conditions and bed-modulated ice flow, with potential impacts on terminus behavior and ice-shelf mass balance. While contemporary observations reveal the presence of basal water movement in the subglacial environment and inferred styles of drainage, the geological record of former ice sheets, including sediments and landforms on land and the seafloor, aids in understanding the spatiotemporal evolution of efficient and inefficient drainage systems and their impact on ice-sheet behavior. We highlight the past decade of advances in geological studies that focus on providing process-based information on subglacial hydrology of ice sheets, how these studies inform theory, numerical models and contemporary observations, and address the needs for future research.
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