| 1. |
- Arja, Katriann, et al.
(författare)
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Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand
- 2013
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Ingår i: Macromolecular rapid communications. - : Wiley-VCH Verlag. - 1022-1336 .- 1521-3927. ; 34:9, s. 723-730
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescent probes identifying protein aggregates are of great interest, as deposition of aggregated proteins is associated with many devastating diseases. Here, we report that a fluorescent amyloid ligand composed of two distinct molecular moieties, an amyloidophilic pentameric oligothiophene and a porphyrin, can be utilized for spectral and lifetime imaging assessment of recombinant A 1-42 amyloid fibrils and A deposits in brain tissue sections from a transgenic mouse model with Alzheimers disease pathology. The enhanced spectral range and distinct lifetime diversity of this novel oligothiopheneporphyrin-based ligand allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye.
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| 2. |
- Borota, Ljubisa, et al.
(författare)
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Spot fluoroscopy : a novel innovative approach to reduce radiation dose in neurointerventional procedures
- 2017
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 58:5, s. 600-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased interest in radiation dose reduction in neurointerventional procedures has led to the development of a method called "spot fluoroscopy" (SF), which enables the operator to collimate a rectangular or square region of interest anywhere within the general field of view. This has potential advantages over conventional collimation, which is limited to symmetric collimation centered over the field of view.PURPOSE: To evaluate the effect of SF on the radiation dose.MATERIAL AND METHODS: Thirty-five patients with intracranial aneurysms were treated with endovascular coiling. SF was used in 16 patients and conventional fluoroscopy in 19. The following parameters were analyzed: the total fluoroscopic time, the total air kerma, the total fluoroscopic dose-area product, and the fluoroscopic dose-area product rate. Statistical differences were determined using the Welch's t-test.RESULTS: The use of SF led to a reduction of 50% of the total fluoroscopic dose-area product (CF = 106.21 Gycm(2), SD = 99.06 Gycm(2) versus SF = 51.80 Gycm(2), SD = 21.03 Gycm(2), p = 0.003884) and significant reduction of the total fluoroscopic dose-area product rate (CF = 1.42 Gycm(2)/min, SD = 0.57 Gycm(2)/s versus SF = 0.83 Gycm(2)/min, SD = 0.37 Gycm(2)/min, p = 0.00106). The use of SF did not lead to an increase in fluoroscopy time or an increase in total fluoroscopic cumulative air kerma, regardless of collimation.CONCLUSION: The SF function is a new and promising tool for reduction of the radiation dose during neurointerventional procedures.
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| 3. |
- Condén, Emelie, 1979-, et al.
(författare)
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Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients?
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 24:5, s. 522-533
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design: This was a prospective cohort study. Methods: Utilising data from the Vastmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results: In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions: No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.
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| 4. |
- Condén, Emelie, 1979-, et al.
(författare)
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Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population
- 2014
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 55:6, s. 601-610
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the prevalence of Type D personality and the temporal stability, internal consistency, and construct validity of the DS14 at three time points after myocardial infarction. The prevalence of Type D personality was 14.0% during hospitalization, 25.1% at 1 month, and 19.2% at 12 months. A total of 6.1% of patients were classified as Type D personality at all three assessments, whereas 68.4% were stable non-Type D and 25.6% changed between personality classifications. The DS14 had stable structural validity, but low temporal stability over time, especially from hospitalization to the 1-month and 12-month follow-ups (k = 0.365 and 0.397, respectively).
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| 5. |
- Gyllenhammar, Andreas, et al.
(författare)
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Flodpärlmussla, Resultat från inventeringarna 1996-2005
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna rapport redovisas de insatser som gjorts för att kartlägga Jämtlands läns bestånd av flodpärlmussla (Margaritifera margaritifera). En kartläggning av historiska bestånd har gjorts, mestadels baserad på litteraturstudier. I rapporten redovisas resultaten från det inventeringsarbete som utförts av Länsstyrelsen i Jämtlands län åren 1996-2005. Resultaten presenteras i form av kartor, figurer och tabeller där beståndens geografiska lokalisering, storlek och reproduktionsstatus redovisas. Länet har idag 53 lokaler med bestånd av flodpärlmussla. I 30 stycken av dessa bestånd förekommer reproduktion men i över hälften (18st) är reproduktionen svag. 12 av bestånden har ett uppskattat individantal på över 10000 individer. Jämtland har i dagsläget Sveriges största bestånd av flodpärlmussla. I Storån, norr om Hammerdal, har antalet individer beräknats till 4,5 miljoner. En mer omfattande analys av läget för flodpärlmusslan i länet kommer att göras då inventeringsmaterialet datalagts i större omfattning och då ytterligare miljödata finns sammanställda. Slutsatserna pekar på vikten av att ytterligare miljödata tillgängliggörs för att möjliggöra en fördjupad analys av musselbeståndens och omgivningsparametrarnas status. Slutligen presenteras hur Länsstyrelsens arbete med flodpärlmussla kommer att fortskrida under 2006, med bl a utformning av ett miljöövervakningsprogram och planering av skyddsåtgärder.
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| 6. |
- Hammarström, Per, et al.
(författare)
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A Fluorescent Pentameric Thiophene Derivative Detects in Vitro-Formed Prefibrillar Protein Aggregates
- 2010
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Ingår i: BIOCHEMISTRY. - : ACS American Chemical Society. - 0006-2960 .- 1520-4995. ; 49:32, s. 6838-6845
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Tidskriftsartikel (refereegranskat)abstract
- Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of their likely role in the mechanism of fibril formation and because of the growing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. Herein, we explore the use of an anionic oligothiophene derivative, p-FTAA, for detection of prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins (insulin, lysozyme, and prion protein). p-FTAA generally detected prefibrillar protein aggregates that could not be detected by thioflavine T fluorescence and in addition showed high fluorescence when bound to mature fibrils. Second, the kinetics of protein aggregation or the formation of amyloid fibrils of insulin was not extensively influenced by the presence of various concentrations of p-FTAA. These results establish the use of p-FTAA as an additional tool for studying the process of protein aggregation.
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| 7. |
- Heilbronner, Goetz, et al.
(författare)
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Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice
- 2013
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Ingår i: EMBO Reports. - : NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND. - 1469-221X .- 1469-3178. ; 14:11, s. 1017-1022
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Tidskriftsartikel (refereegranskat)abstract
- The polymorphic beta-amyloid lesions present in individuals with Alzheimers disease are collectively known as cerebral beta-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop beta-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and A beta 40/A beta 42 peptide ratio. To determine the nature of such beta-amyloid morphotypes, beta-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced beta-amyloid deposition with the morphological, conformational, and A beta 40/A beta 42 ratio characteristics of beta-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced b-amyloid deposits with the characteristics of beta-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced beta-amyloid deposits, although less prominent, and the induced deposits were similar to the beta-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated A beta in APP transgenic mice can be maintained by seeded conversion.
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| 8. |
- Herrmann, Uli S., et al.
(författare)
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Structure-based drug design identifies polythiophenes as antiprion compounds
- 2015
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:299, s. 299ra123-
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Tidskriftsartikel (refereegranskat)abstract
- Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrPSc, a misfolded and aggregated form of the cellular prion protein (PrPC). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by greater than80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.
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| 9. |
- Ilkhanizadeh, Shirin, et al.
(författare)
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Live Detection of Neural Progenitors and Glioblastoma Cells by an Oligothiophene Derivative
- 2023
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 6:9, s. 3790-3797
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
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| 10. |
- Johansson, Leif B. G., et al.
(författare)
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An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates
- 2015
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 63, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.
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