| 1. |
- Abu Hamdeh, Sami, et al.
(författare)
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Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury
- 2018
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Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 28:4, s. 451-462
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Tidskriftsartikel (refereegranskat)abstract
- Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n = 5), to post-mortem tissue of neurologically intact (NI) subjects (n = 4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n = 4). The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to NI and iNPH controls (P < 0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n = 4) had increased levels of Aβ oligomers/protofibrils (P < 0.05) and of both N-terminally intact and truncated Aβ42 (P < 0.05) compared to APOE ε3/4-negative TBI patients (n = 8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers. We conclude that soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI.
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| 2. |
- Blomberg, Anders, et al.
(författare)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 3. |
- Boström, Hans, et al.
(författare)
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U-2973, a novel B-cell line established from a patient with a mature B-cell leukemia displaying concurrent t(14;18) and MYC translocation to a non-IG gene partner
- 2008
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 81:3, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- B-cell lymphomas/leukemias with simultaneous t(14;18)(q32;q21) and MYC rearrangements have recently been shown to constitute a separate diagnostic entity, presenting with a rapid clinical course and a very poor prognosis. We describe the establishment of an Epstein-Barr virus negative cell line, designated U-2973, from a male patient with a de novo aggressive B-cell lymphoma/leukemia and very high peripheral blast cell count. Flow cytometry of bone marrow cells and U-2973 displayed a mature B-cell phenotype, and immunostaining showed expression of MYC and BCL2. IG gene rearrangement data were consistent with a lymphoid neoplasm of germinal centre derivation. Cytogenetic studies using conventional G-banding, fluorescent in situ hybridization, spectral karyotyping and single nucleotide polymorphism array demonstrated a complex karyotype with both a t(14;18) and double translocations between MYC and a non-IG gene partner located at chromosome 12p12.1.
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| 4. |
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| 5. |
- Dyhre, Henrik, et al.
(författare)
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Local anesthetics in lipid-depot formulations--neurotoxicity in relation to duration of effect in a rat model
- 2006
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Ingår i: Regional anesthesia and pain medicine. - : BMJ. - 1098-7339 .- 1532-8651. ; 31:5, s. 401-408
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the possible local neurotoxicity of a number of lipid-depot formulations of local anesthetics in relation to their duration of action in sciatic-nerve block. METHODS: Formulations that contain 2%, 4%, 8%, 16%, 32%, or 64% of a mixture of bupivacaine and lidocaine base 4:1 in medium-chain triglyceride were prepared and evaluated, together with 0.5%, 1.0%, and 2.0% bupivacaine HCl solutions, bupivacaine 4.2% or 7.0% in medium-chain triglyceride, and 20% lidocaine base in a polar lipid vehicle. The duration of sensory and motor sciatic-nerve block was determined in rats. A week later, the sciatic nerves were dissected and removed for histopathologic examination by light microscopy. RESULTS: The duration of sensory and motor-nerve block was prolonged almost 4 times with the 32% and 13 times with the 64% bupivacaine:lidocaine formulation, in comparison to the 0.5% aqueous solution. The 64% formulation was applied by injection and also placed directly on the nerve with similar results. Slight to moderate signs of neurotoxicity were only found after administration of the 64% formulation. CONCLUSIONS: The findings suggest that depot formulations of local anesthetics with advantageous pharmaceutical and pharmacologic properties can be prepared by use of bupivacaine as the active component and natural lipids as carriers. A favorable balance between effects and toxicity may conceivably be obtained. After supplemental testing in more sensitive models for toxicity, such formulations could be candidates for clinical trials.
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| 6. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 7. |
- Frödin, Kerstin, 1971-
(musiker, creator_code:cre_t)
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Hidden voices : by Lipparella
- 2021
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Konstnärligt arbete (refereegranskat)abstract
- Album by the ensemble Lipparella.Lipparella performs music byChrichan Larson - Czarne Latawce (2013) Madeleine Isaksson - Hemligheten (2013)Christer Lindwall - What is the word (2018-19Lipparella: Louise Agnani - viola da gamba Mikael Bellini - counter tenorKerstin Frödin - recordersAnna Lindal - violin Peter Söderberg - theorbo Tracks:Czarne Latawce: I. 01:12Czarne Latawce: II. 01:01Czarne Latawce: III. 00:48Czarne Latawce: IV. 04:13Czarne Latawce: V. 03:21Czarne Latawce: VI. 00:40Czarne Latawce: VII. 03:29Czarne Latawce: VIII. 01:47Hemligheten: I. 03:23Hemligheten: II. 00:48Hemligheten: III. 03:13Hemligheten: IV. 04:16Hemligheten: V. 01:57Hemligheten: VI. 01:55Hemligheten: VII. 04:05What Is the Word 22:10
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| 8. |
- Gkanatsiou, Eleni, et al.
(författare)
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Characterization of monomeric and soluble aggregated Aβ in Down's syndrome and Alzheimer's disease brains.
- 2021
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Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 754
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Tidskriftsartikel (refereegranskat)abstract
- The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (Aβ) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Our aim was to investigate the Aβ peptide pattern in DS and AD brains to investigate differences in their amyloid deposition and aggregation, respectively. Cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (water soluble) and formic acid (water insoluble) fractions. Immunoprecipitation (IP) was performed using a variety of antibodies targeting different Aβ species including oligomeric Aβ. Mass spectrometry was then used to evaluate the presence of Aβ species in the different patient groups. A large number of Aβ peptides were identified including Aβ1-X, 2-X, 3-X, 4-X, 5-X, 11-X, and Aβ peptides extended N terminally of the BACE1 cleavage site and ending at amino 15 in the Aβ sequence APP/Aβ(-X to 15), as well as peptides post-translationally modified by pyroglutamate formation. Most Aβ peptides had higher abundance in AD and DS compared to controls, except the APP/Aβ(-X to 15) peptides which were most abundant in DS followed by controls and AD. Furthermore, the abundancies of AβX-40 and AβX-34 were increased in DS compared with AD. Aβ1-40, Aβ1-42, and Aβ4-42 were identified as the main constitutes of protofibrils (IP'd using mAb158) and higher relative Aβ1-42 signals were obtained compared with samples IP'd with 6E10+4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at amino acid 42. All Aβ peptides found in AD were also present in DS indicating similar pathways of Aβ peptide production, degradation and accumulation, except for APP/Aβ(-X to 15). Likewise, the Aβ peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility that treatment with clinical benefit in sporadic AD might also be beneficial for subjects with DS.
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| 9. |
- Grannas, Karin, 1983-
(författare)
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Improvements and Applications of in situ Proximity Ligation Assays
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cells building up the human body is in constant communication with each other. This communication is done through large complex networks of signaling pathways for inter- and intracellular signal transduction. The signaling activity regulates many important processes, for example cell death, proliferation and differentiation. Information within the signaling networks is communicated over the cell membrane, through the cytoplasm and entering the nucleus by protein activities such as protein-protein interactions (PPIs) and post translation modifications (PTMs). The cells adapts to their own environment, responding to multiple stimuli from their surroundings. This in combination with memory of previous responses, difference in cell cycles stages and sometimes altered genetic background generates heterogeneous cell populations in which every cell is slightly different from its neighbor. This calls for methods to study the activity of endogenous proteins in individual cells within a population.In situ proximity ligation assay (in situ PLA) was originally developed to visualize interaction between endogenous proteins in fixed cells and tissue and can also be applied to detect PTMs. This thesis describe the application of in situ PLA to study PPIs in signaling pathways and the work to further develop and improve techniques for proximity dependent detection. In paper I in situ PLA is used to study cross talk between the Hippo and the TGFβ signaling pathways. The study shows the complex formation by the transcription co-factors of the Hippo pathway, Yap and Taz, and the main effectors of the TGFβ pathway Smad2/3. Furthermore the density dependent localization of the interaction is described.Paper II presents a new version of the in situ PLA probes for simultaneous detection of multiple complexes. Visualization of various complexes involving EGFR, Her2 and Her3 is presented as a proof of concept.The efficiency of in situ PLA is limited by several factors, one being the design of PLA probes and oligonucleotide systems. Even upon proximal binding of the probes there is a risk of formation of non-circular ligation products, which cannot be amplified and detected. In Paper III two new PLA probes are presented aiming to reduce the formation of non-circular ligation product and hence increase the detection efficiency of in situ PLA.Paper IV presents a new method for detection of protein complexes and phosphorylation; proxHCR. ProxHCR combines signal amplification by enzyme free hybridization chain reaction (HCR) with the requirement of proximal binding of two affinity probes. As a proof of principle the method is used to detect multiple complexes and protein phosphorylation in fixed cells and tissue.
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| 10. |
- Grimm, Alejandro, et al.
(författare)
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Slagging and fouling characteristics during co-combustion of Scots pine bark with low-temperature dried pulp and paper mill chemical sludge
- 2019
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Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 193, s. 282-294
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Tidskriftsartikel (refereegranskat)abstract
- This paper shows how chemical sludge (CS) generated during wastewater treatment at a paperboard mill can be quickly dried at low-temperature and employed in bark-fired boilers to reduce slagging and corrosion problems. By using a cyclone-dryer operated at an inlet-air velocity of 110 m/s and a temperature of 90 degrees C, the dry-matter content of CS was increased from approximately 19 to 82%. The residence time of CS inside the cyclone was approximately 2 s when using the inlet-air velocity mentioned above. Disaggregation of the feedstock caused by collisions with the cyclone wall and between particles played a crucial role in enhancing the efficiency of heat and mass transfer. Three co-pelletized mixtures of Scots pine bark (SPB) and dried-CS were combusted in a 40 kW fixed-bed burner. Flue gas analysis was performed with a gas analyser. Coarse and fine ash were analysed by SEM-EDS and XRD. NOx, and SO2 emissions increased with increasing amount of CS in the mixtures. Mono combustion of SPB resulted in a large quantity of slag (i.e., molten ash) with a high degree of sintering (i.e., hardness of the slag), and ash deposits formed on heat transfer surfaces were rich in K2SO4 and KCI. Mixtures of SPB and CS were less prone to slagging, and the amount of alkali chloride in the deposits was reduced in favour of alkali sulphate formation.
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