| 1. |
- Pendleton, Hillevi, et al.
(författare)
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Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus.
- 2009
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Ingår i: European journal of internal medicine. - : Elsevier BV. - 1879-0828 .- 0953-6205. ; 20:6, s. 654-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Dysmotility in the upper gastro intestinal (GI) tract are common problems in diabetics. Many peptides are involved in the regulation of the motility. The aim of this study was to examine whether plasma levels of motilin were related to dysfunction in the oesophagus and stomach in a well-defined diabetic patient group. METHODS: Nineteen patients with symptoms from the GI tract who had been examined with oesophageal manometry, gastric emptying scintigraphy and deep-breathing test were included. They received a fat-rich meal, after which blood samples were collected and analysed for motilin concentrations. RESULTS: Symptoms of abdominal fullness and gastro oesophageal reflux significantly associated with delayed gastric emptying, whereas no symptom correlated to oesophageal dysmotility. Plasma levels of motilin were increased after the fat-rich meal (p=0.000), with no difference between the groups. Abnormal manometry was characterized by aperistalsis and/or simultaneous contractions. The percentage of simultaneous contractions correlated to basic and peak motilin values (r(s)=0.898, p=0.006 and r(s)=0.842, p=0.017, respectively). Gastric emptying did not influence motilin concentrations. CONCLUSION: Plasma motilin concentrations vary with abnormalities of oesophageal motility in diabetics, but not with abnormalities of gastric emptying.
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| 2. |
- Aardal-Eriksson, Elisabeth
(författare)
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Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
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| 3. |
- Ambrus, Livia, et al.
(författare)
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Plasma Brain-Derived Neurotrophic Factor and Psychopathology in Attempted Suicide
- 2016
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 73:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Increasing evidence suggests a link between brain-derived neurotrophic factor (BDNF) and suicidal behaviour (SB). Furthermore, decreased peripheral BDNF levels have been associated with clinical symptoms in various psychiatric disorders as well as with personality dimensions in healthy individuals. However, the relationship between BDNF and psychopathology is poorly investigated regarding SB. Methods: Plasma BDNF concentrations were analysed in 61 recent suicide attempters. Clinical symptoms were evaluated using the Comprehensive Psychopathological Rating Scale. Personality dimensions were assessed using the Marke-Nyman Temperament Scale. Results: Plasma BDNF correlated positively and significantly with the personality dimension Solidity but not with the other personality dimensions or with clinical symptoms. Conclusion: BDNF plays an important role in the regulation of neuroplasticity and neurogenesis in humans. Our results indicate that lower BDNF concentrations are associated with higher levels of impulsiveness and changeability (low scores on the Solidity scale). Furthermore, low plasma BDNF levels may be proposed as a trait marker rather than a state marker for attempted suicide. (C) 2016 S. Karger AG, Basel
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| 4. |
- Asberg, Marie, et al.
(författare)
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Novel biochemical markers of psychosocial stress in women.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.
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| 5. |
- Axelsson, John, et al.
(författare)
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Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/T Helper 2 Balance in Humans
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. BAS AK, 1991, IMMUNOLOGICAL REVIEWS, V123, P5
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| 6. |
- Banijamali, Mahsan, et al.
(författare)
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Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis
- 2022
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Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Small extracellular vesicles (sEVs) have in recent years evolved as a source of biomarkers for disease diagnosis and therapeutic follow up. sEV samples derived from multicellular organisms exhibit a high heterogeneous repertoire of vesicles which current methods based on ensemble measurements cannot capture. In this work we present droplet barcode sequencing for protein analysis (DBS-Pro) to profile surface proteins on individual sEVs, facilitating identification of sEV-subtypes within and between samples. The method allows for analysis of multiple proteins through use of DNA barcoded affinity reagents and sequencing as readout. High throughput single vesicle profiling is enabled through compartmentalization of individual sEVs in emulsion droplets followed by droplet barcoding through PCR. In this proof-of-concept study we demonstrate that DBS-Pro allows for analysis of single sEVs, with a mixing rate below 2%. A total of over 120,000 individual sEVs obtained from a NSCLC cell line and from malignant pleural effusion (MPE) fluid of NSCLC patients have been analyzed based on their surface proteins. We also show that the method enables single vesicle surface protein profiling and by extension characterization of sEV-subtypes, which is essential to identify the cellular origin of vesicles in heterogenous samples.
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| 7. |
- Bergquist, Jonas, et al.
(författare)
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Future aspects of psychoneuroimmunology - lymphocyte peptides reflecting psychiatric disorders studied by mass spectrometry
- 2001
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Ingår i: Archives of Physiology and Biochemistry. - 1381-3455 .- 1744-4160. ; 109:4, s. 369-371
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated whether cytoplasmatic and nuclear extracts of human peripheral blood lymphocytes contain arginine vasopressin (AVP), of importance for memory functions, in samples from healthy controls and patients diagnosed as depressed. It is the first time as AVP, AVP-fragments and chemically modified AVP-forms have been demonstrated in lymphocyte/nuclear extracts. This was performed by an HPLC-purification step, followed by a second immunoprecipitation step before identification by mass spectrometry. We are developing new methods using a combination of high-resolution mass spectrometry and separation techniques such as capillary electrophoresis and nano liquid chromatography. We have named this methodological approach when studying endogenous peptides -Peptidomics.
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| 8. |
- Bergquist, Jonas, et al.
(författare)
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New Approaches to Neurochemistry
- 2009
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Ingår i: Mass Spectrometry. - : John Wiley & Sons, Inc.. - 9780471713951 ; , s. 321-335
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Björklund, Lars-Erik, 1953-
(författare)
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Från novis till expert : förtrogenhetskunskap i kognitiv och didaktisk belysning
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med den här avhandlingen är att bidra till förståelsen av beprövad erfarenhetsbaserad kunskap, det vi förknippar med fårdigheter, förmågor och förtrogenhet. Avhandlingen är enintegrerande forskningsöversikt, fntegrative research review. Genom att sammanställa, jämföra och integrera resultat från psykologins, beteendevetenskapens, neuromedicinens och neurofysiologins forskningsfålt synliggör författaren en neurodidaktisk modell för hur experters egenskaper och förmågor byggs upp under praktisk erfarenhet i en specifik kontext.När en engagerad individ utsätts för en upprepad variation av upplevelser skapas kunskap som består av utfallsmärkta sensoriska mönster i framför allt de basala ganglierna men även i amygdala och cerebellum. Dessa sammantaget utgör ett implicit, omedvetet inlärningssystem parallellt med det medvetna explicita. Det implicita systemet jämför det vi betraktar med tidigare lagrade mönster vilket gör att vi snabbt kan upptäcka vad som är relevant i komplexa, stressade situationer. Med dess hjälp blir vi mer kompetenta i vår roll som lärare, hantverkare, läkare etc. Den här kunskapen blir omedveten, dold och tyst, det som Polanyi kallar Tacit knowledge och som bröderna Dreyfus refererar till som holistic pattern recognition. När vårt medvetande uppmärksammar ett igenkännande i det implicita systemet upplever vi en känsla, intuition eller gut feeling. Det implicita bedömningssystemet hämmas inte av arbetsminnets begränsningar i hastighet och antal detaljer och blir med tiden en resurs som visar sig som förtrogenhet inom en praktik. Mycket talar för att de mönster och erfarenheter som lagras i det implicita systemet används vid problemlösning. Detta leder till implikationer för hur undervisning och lärandemiljöer i exempelvis teknikämnet ska planeras för att befrämja en kreativ utveckling hos den lärande.Det implicita systemet ger oss en omedveten kapacitet att tolka andra människors kroppsspråk och aktiveras av kända kontexter och artefakter. Detta påverkar de svar vi som forskare får från våra informanter i en intervjusituation. För att nå expertens tysta kunskap om t.ex. bedömningskriterier kan en speciell intervjumetod; Repertory Grid Technique, användas.
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| 10. |
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| 11. |
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| 12. |
- Cavallaro, Sara, et al.
(författare)
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Multiplexed electrokinetic sensor for detection and therapy monitoring of extracellular vesicles from liquid biopsies of non-small-cell lung cancer patients
- 2021
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Liquid biopsies based on extracellular vesicles (EVs) represent a promising tool for treatment monitoring of tumors, including non-small-cell lung cancers (NSCLC). In this study, we report on a multiplexed electrokinetic sensor for surface protein profiling of EVs from clinical samples. The method detects the difference in the streaming current generated by EV binding to the surface of a functionalized microcapillary, thereby estimating the expression level of a marker. Using multiple microchannels functionalized with different antibodies in a parallel fluidic connection, we first demonstrate the capacity for simultaneous detection of multiple surface markers in small EVs (sEVs) from NSCLC cells. To investigate the prospects of liquid biopsies based on EVs, we then apply the method to profile sEVs isolated from the pleural effusion (PE) fluids of five NSCLC patients with different genomic alterations (ALK, KRAS or EGFR) and applied treatments (chemotherapy, EGFR- or ALKtyrosine kinase inhibitors). The vesicles were targeted against CD9, as well as EGFR and PD-L1, two treatment targets in NSCLC. The electrokinetic signals show detection of these markers on sEVs, highlighting distinct interpatient differences, e.g., increased EGFR levels in sEVs from a patient with EGFR mutation as compared to an ALK-fusion one. The sensors also detect differences in PD-L1 expressions. The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1). These results hold promise for the application of the method for tumor treatment monitoring based on sEVs from patient liquid biopsies.
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| 13. |
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| 14. |
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| 15. |
- Davidsson, Pia, 1962, et al.
(författare)
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Clinical mass spectrometry in neuroscience. Proteomics and peptidomics.
- 2003
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Ingår i: Cellular and molecular biology (Noisy-le-Grand, France). - 0145-5680 .- 1165-158X. ; 49:5, s. 681-8
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Forskningsöversikt (refereegranskat)abstract
- In this review we discuss the merits and drawbacks with the use of proteomic and peptidomic strategies for identification of proteins and peptides in their multidimensional interactions in complex biological processes. The progress in proteomics and peptidomics during the last years offer us new challenges to study changes in the protein and peptide synthesis. These strategies also offer new tools to follow post-translational modifications and other disturbed chemical processes that may be indicative of pathophysiological alteration(s). Furthermore these techniques can contribute to improvements in the diagnosis and therapy of neurodegenerative diseases, such as Alzheimer's disease, and psychiatric diseases, as depression and post traumatic stress disorders. We also consider different practical aspects of the applications of mass spectrometry in clinical neuroscience, illustrated by example from our laboratories. The new proteomic and peptidomic strategies will further enable the progress for clinical neuroscience research.
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| 16. |
- Dimberg, Lina Y., et al.
(författare)
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Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 318-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods: To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). Results: To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion: We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Ekman, Rolf, 1938, et al.
(författare)
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A flourishing brain in the 21st century: A scoping review of the impact of developing good habits for mind, brain, well-being, and learning
- 2022
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Ingår i: Journal of Mind, Brain and Education. - : Wiley. - 1751-228X .- 1751-2271. ; 16:1, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- Emerging scientific knowledge such as the role of epigenetics and neuroplasticity—the brain’s capability to constantly rewire with every action, experience, and thought—is fundamentally changing our understanding of the potential impact we can have on our brain. Our brain is formed by our habits in interaction with our body, the environment, influenced by our lifestyle, successes, failures, and traumas. Neuroplasticity proves that every student’s brain is a work in progress, and it is never too late to take better care of one’s cognitive fitness. This review presents a repertoire of good habits (GHs). Combined, we suggest that these GHs provide conditions for optimal brain health, by acting as a “Mental Vaccine” which enhances the brain’s resilience to brain health-degrading challenges. We argue hat schools have a crucial role to play in empowering students to increase their own stress resilience, well-being, and learning by developing their own GHs profile.
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| 21. |
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| 22. |
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| 23. |
- Ekman, Rolf, 1938, et al.
(författare)
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Den lärande hjärnan i den digitala tidsåldern
- 2011
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Ingår i: Lärandets grunder - teorier och perspektiv. - Lund : Studentlitteratur. - 9789144068503
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
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| 25. |
- Ekström, Jörgen, 1944, et al.
(författare)
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Sympathectomy-induced increases in calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide (VIP)-levels in parotid and submandibular glands of the rat
- 2005
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Ingår i: Arch Oral Biol. ; 50:10, s. 909-17
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide contents of rat salivary glands were increased four weeks after sympathetic postganglionic denervation (but not after preganglionic denervation): calcitonin gene-related peptide (CGRP) by 400 and 65% in the parotid and submandibular glands, respectively; substance P by 30% in the submandibular gland; and vasoactive intestinal peptide (VIP) by 30% in the parotid gland. The sensory neurotoxin capsaicin prevented the expected increases of CGRP and substance P in the submandibular glands and of VIP in the parotid glands. The CGRP-increase in the parotid gland was, however, only reduced (by 65%). Parasympathetic otic ganglionectomy reduced the peptide levels in the parotid glands (CGRP--50%, VIP--98% and substance P--99%). From these residual levels, CGRP increased almost 8-fold and substance P 3-fold in response to the sympathetic denervation, while VIP was unaffected. In the parasympathetically denervated glands, the capsaicin-sensitive contribution to the CGRP-response to sympathetic denervation was roughly estimated to be more than 25% but less than 40%, while the corresponding contribution to the substance P-response was roughly estimated to be more than 6% but less than 58%. Most likely not only CGRP/substance P-containing sensory C-fibres (submandibular and parotid glands) but also parasympathetic VIP-containing secretomotor and vasomotor fibres (parotid glands) contributed to the capsaicin-sensitive response to sympathetic denervation.
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| 26. |
- Elias, Erik, 1979, et al.
(författare)
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Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.
- 2011
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 23:6, s. 501-7
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Tidskriftsartikel (refereegranskat)abstract
- Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ=0.695, P<0.001, n=26) and galanin (ρ=0.651, P<0.001) as well as visceral adipose tissue (ρ=0.415, P=0.035). Furthermore, CSF L-PGDS was inversely correlated with CSF leptin (ρ=-0.529, P=0.005) and tended to correlate inversely with s.c. adipose tissue (ρ=-0.346, P=0.084). As reported earlier, leptin treatment had no effect on weight loss and did not affect CSF L-PGDS or NPY levels compared to placebo. After weight loss, the change of CSF L-PGDS was significantly correlated with the change of CSF NPY levels (ρ=0.604, P=0.004, n=21). Because of the correlation between baseline CSF L-PGDS levels and visceral adipose tissue, we examined associations with hypothalamic-pituitary-adrenal (HPA) axis components. Baseline CSF L-PGDS was correlated with corticotrophin-releasing hormone (ρ=0.764, P<0.001) and β-endorphin (ρ=0.491, P<0.001). By contrast, serum L-PGDS was not correlated with any of the measured variables either at baseline or after treatment. In summary, CSF L-PGDS was correlated with orexigenic neuropeptides, visceral fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.
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| 27. |
- Erlinge, David, et al.
(författare)
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Neuropeptide Y-like immunoreactivity and hypertension
- 1992
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Ingår i: Journal of Hypertension. - 1473-5598. ; 10:10, s. 1221-1225
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Neuropeptide Y is a co-transmitter with noradrenaline in sympathetic neurons supplying arteries and veins with potent contractile effects. To investigate the role of neuropeptide Y in hypertension, we measured the circulating levels of neuropeptide Y and noradrenaline in patients with severe hypertension. DESIGN: Samples were collected from patients with untreated, severe hypertension (diastolic blood pressure > 120 mmHg) and in age- and sex-matched controls. After treatment with beta-adrenoceptor blockers, diuretics, angiotensin converting enzyme inhibitors of calcium antagonists, samples were taken from the patients during 12 months. METHODS: The circulating levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured with a radioimmunoassay using a rabbit antiserum. Catecholamines were measured using high-performance liquid chromatography and electrochemical detection. RESULTS: There was a significantly higher level of NPY-LI in the patients when they were compared with the controls. However, there was no correlation either in the controls or in the hypertensives between systolic blood pressure, diastolic blood pressure and NPY-LI or noradrenaline. The increased level of NPY-LI in plasma remained elevated for up to 12 months despite reduction in blood pressure to acceptable levels. The noradrenaline level was not increased before treatment, after 2-4 weeks or after 2-12 months treatment. CONCLUSION: The high level of NPY-LI may represent a marker for higher activity of the sympathetic nervous system which is not controlled by the treatment of blood pressure to normotension.
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| 28. |
- Fouassier, Laura, et al.
(författare)
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Ezrin-radixin-moesin-binding phosphoprotein (EBP50), an estrogen-inducible scaffold protein, contributes to biliary epithelial cell proliferation.
- 2009
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 174:3, s. 869-80
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Tidskriftsartikel (refereegranskat)abstract
- Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ie, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats and Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent up-regulation and intracellular redistribution in response to 17beta-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells.
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| 29. |
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| 30. |
- Gustafsson, Gunnar, et al.
(författare)
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The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.
- 2009
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 169:3, s. 244-248
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between plasma plasma-BDNF levels, dexamethasone suppression test cortisol levels and Montgomery-Asberg Depression Rating Scale (MADRS) scores were also tested. No difference in basal BDNF levels between patients and controls was found. BDNF increased significantly during exercise in both male and female patients as well as in male controls, with no significant differences between the groups. BDNF levels declined after exercise, but after 60 min of rest BDNF levels showed tendencies to increase again in male patients. No correlation between BDNF and cortisol or MADRS scores was found. We conclude that unmedicated patients with moderate depression and normal activity of the hypothalamic-pituitary-adrenal axis do not have a disturbed peripheral BDNF release during exercise. The BDNF increase 60 min after interruption of exercise in male patients might indicate up-regulated BDNF synthesis, but this needs to be further investigated in future studies.
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| 31. |
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| 32. |
- Henricson, Maria, 1972-, et al.
(författare)
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The outcome of tactile touch on oxytocin in intensive care patients : a randomized controlled trial
- 2008
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 17:19, s. 2624-2633
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Tidskriftsartikel (refereegranskat)abstract
- Aim. To explore the effects of five-day tactile touch intervention on oxytocin in intensive care patients. The hypotheses were that tactile touch increases the levels of oxytocin after intervention and over a six-day period. Background. Research on both humans and animals shows a correlation between touch and increased levels of oxytocin which inspired us to measure the levels of oxytocin in arterial blood to obtain information about the physiological effect of tactile touch. Design. Randomised controlled trial. Method. Forty-four patients from two general intensive care units, were randomly assigned to either tactile touch ( n = 21) or standard treatment – an hour of rest ( n = 23). Arterial blood was drawn for measurement of oxytocin, before and after both treatments. Results. No significant mean changes in oxytocin levels were found from day 1 to day 6 in the intervention group (mean −3·0 pM, SD 16·8). In the control group, there was a significant ( p = 0·01) decrease in oxytocin levels from day 1 to day 6, mean 26·4 pM (SD 74·1). There were no significant differences in changes between day 1 and day 6 when comparing the intervention group and control group, mean 23·4 pM (95% CI −20·2–67·0). Conclusion. Our hypothesis that tactile touch increases the levels of oxytocin in patients at intensive care units was not confirmed. An interesting observation was the decrease levels of oxytocin over the six-day period in the control group, which was not observed in the intervention group. Relevance to clinical practice. Tactile touch seemed to reduce the activity of the sympathetic nervous system. Further and larger studies are needed in intensive care units to confirm/evaluate tactile touch as a complementary caring act for critically ill patients.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Monocyte chemotactic protein-1 (MCP-1) and growth factors called into question as markers of prolonged psychosocial stress.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS: Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE: MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured.
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| 37. |
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| 38. |
- Khosravani, Nina, et al.
(författare)
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The peptidergic innervation of the rat parotid gland: effects of section of the auriculo-temporal nerve and/or of otic ganglionectomy.
- 2008
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Ingår i: Archives of oral biology. - : Elsevier BV. - 0003-9969. ; 53:3, s. 238-42
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Tidskriftsartikel (refereegranskat)abstract
- The origin/pathways of peptidergic nerves contributing to the parotid gland contents of vasoactive intestinal peptide (VIP), substance P and calcitonin gene-related peptide (CGRP) were investigated by performing surgery on one side of the rat. Comparisons (based on total amount of peptide) were made between the gland on the operated side and the contralateral gland 7 days postoperatively. Otic ganglionectomy showed that almost all of the parotid gland contents of VIP (98%) and substance P (98%) were due to the otic connection, while this was true for only a minor portion (32%) of the CGRP-gland content. Section of the auriculo-temporal nerve showed that almost all of the VIP- and substance P-containing nerve fibres reached the parotid gland via this nerve, as judged by a reduction in the VIP-content by 88% and in the substance P-content by 93%, while the CGRP-content was only reduced by 37%. Section of the auriculo-temporal nerve combined with otic ganglionectomy did not reduce the gland contents of CGRP and substance P further than just otic ganglionectomy. Thus, the auriculo-temporal nerve is not likely to innervate the parotid gland with CGRP- and/or substance P-containing nerve fibres from the trigeminal ganglion.
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| 39. |
- Kindblom-Rising, Kristina, et al.
(författare)
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Nursing staff's communication modes in patient transfer before and after an educational intervention
- 2010
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 53:10, s. 1217-1227
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to explore and describe nursing staff's body awareness and communication in patient transfers and evaluate any changes made after an educational intervention to promote staff competence in guiding patients to move independently. In total, 63 nursing staff from two hospitals wrote weekly notes before and after the intervention. The topics were: A) reflect on a transfer during the last week that you consider was good and one that was poor; B) reflect on how your body felt during a good and a poor transfer. The notes were analysed with content analysis. The results showed five different communication modes connected with nursing staff's physical and verbal communication. These communication modes changed after 1 year to a more verbal communication, focusing on the patient's mobility. The use of instructions indicated a new or different understanding of patient transfer, which may contribute to a development of nursing staff's competence. Statement of Relevance: The present findings indicate that patient transfer consists of communication. Therefore, verbal and bodily communication can have an integral part of training in patient transfer; furthermore, the educational design of such programmes is important to reach the goal of developing new understanding and enhancing nursing staff's competence in patient transfer.
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| 40. |
- Kindblom-Rising, K., et al.
(författare)
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Nursing staff's perception of changes in patient transfer habits after a course - a phenomenological-hermeneutic study
- 2007
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 50:7, s. 1017-1025
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to illuminate nursing staff's perception of changes after a course in patient transfer. The learning process took the form of self-experience focusing on the manner of supporting the patient to move independently. A total of 20 participants, who had answered a previously administered questionnaire, were chosen for interviews. The themes concerned the meaning of changing transfer habits. A phenomenological-hermeneutic analysis method showed that changes focused on the patient's body, the staff member's own body or cooperation with the patient. Awareness of one's own body and confidence in one's own ability seem to indicate differences in the manner of supporting the patient to move. The changes in transfer habits varied in content and meaning from person to person, depending on the focus during the transfer. These findings can contribute to an understanding of how change takes place after an educational intervention.
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| 41. |
- Lavén, Martin, 1971-
(författare)
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Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices : Exploration of Radiotracer Chemistry as an Analytical Tool
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Liquid chromatography – mass spectrometry (LC-MS) methods were developed for the analysis of positron emission tomography (PET) radiotracers in biological matrices. Additionally, radiotracer chemistry was explored as an analytical tool for supporting LC-MS method development and imaging molecular interactions in miniaturised chemical analysis systems.Conventional radiodetection methods can offer high sensitivity in the analysis of radiotracers in biological matrices, although with the short half-life of PET tracers, this mass sensitivity decreases rapidly with time. This limits the time frame for analysis, and may compromise the precision and accuracy of the later measurements. Performing LC-MS analysis of the dominant stable isotope form of the tracer removes such time restrictions.An LC-MS/MS method was developed for determination of the tracer flumazenil in human plasma, with high inter-assay precision (RSD < 7%) and accuracy (95 – 104%). The method was applied in a multiple scan PET study where the plasma concentration spanned from 0.07 to 0.21 nM. The method removed the time restrictions associated with radiodetection methods and thus provided the opportunity of analysing a greater number of samples than would have been possible with radioanalysis.Furthermore, an LC-MS/MS method was developed that provided an efficient metabolic screening tool of potential PET tracers, whereby the substrates could be collected directly from 11C-labelling batches. This permitted repeated incubation experiments without the need of repeated labelling syntheses. A para-methoxy-benzamide analogue of the radiotracer WAY-100635 was thus identified as a potential tracer with improved metabolic stability. Additionally, a capillary LC-MS method was developed with rapid (0.75 min) and efficient (> 99%) on-line high flow-rate extraction for determination of metabolic stability of PET radiotracers.Finally, the concept of radionuclide imaging of miniaturised chemical analysis systems was demonstrated with the direct study of interactions within capillary extraction columns and microchannels moulded in a plastic CD and poly(dimethylsiloxane).
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| 42. |
- Lekander, Mats, et al.
(författare)
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Subjective health perception in healthy young men changes in response to experimentally restricted sleep and subsequent recovery sleep
- 2013
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 34, s. 43-46
-
Tidskriftsartikel (refereegranskat)abstract
- Sleep and subjective health are both prospectively related to objective indices of health and health care use. Here, we tested whether five days with restricted sleep and subsequent recovery days affect subjective health and is related to increased levels of circulating IL-6 and TNF-alpha and fatigue. Nine healthy men (23-28 years) went through a 6-week sleep protocol with subjects as their own controls in a repeated measures design with a total of 11 nights in a sleep laboratory. The experimental part of the protocol included three baseline days (sleep 23-07 h), five days with sleep restriction (03-07 h) and three recovery days (23-07 h) in the sleep laboratory. Subjective health and fatigue was recorded daily. Eight blood samples were drawn each day (every third hour) on 8 days of the protocol and analyzed with respect to IL-6 and TNF-alpha. Subjective health deteriorated gradually during restricted sleep (p = .002) and returned to baseline levels after three days of recovery. IL-6 and TNF-alpha did not change significantly. Fatigue increased gradually during sleep restriction (p = .001), which significantly contributed to the association between restricted sleep and subjective health. The study is the first to show that subjective health is directly responsive to changes in sleep length and related to increased fatigue. Thus, subjective health is differently appraised after manipulation of one of its presumed determinants. Larger experimental studies would be beneficial to further distinguish causation from association regarding the underpinnings of subjective health. (C) 2013 Published by Elsevier Inc.
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| 43. |
- Lindqvist, C Mårten, et al.
(författare)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
-
Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Nilsson, Christer, et al.
(författare)
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Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine
- 1990
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 27:1, s. 11-26
-
Tidskriftsartikel (refereegranskat)abstract
- Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.
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| 48. |
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| 49. |
- Paulson, Linda, 1971, et al.
(författare)
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Proteomics and peptidomics in neuroscience. Experience of capabilities and limitations in a neurochemical laboratory.
- 2005
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1076-5174 .- 1096-9888. ; 40:2, s. 202-13
-
Forskningsöversikt (refereegranskat)abstract
- The increasing use of proteomics has created a basis for new strategies to develop methodologies for rapid identification of protein patterns in living organisms. It has also become evident that proteomics has other potential applications than protein and peptide identification, e.g. protein characterization, with the aim of revealing their structure, function(s) and interactions of proteins. In comparative proteomics studies, the protein expression of a certain biological system is compared with another system or the same system under perturbed conditions. Global identification of proteins in neuroscience is extremely complex, owing to the limited availability of biological material and very low concentrations of the molecules. Moreover, in addition to proteins, there are number of peptides that must also be considered in global studies on the central nervous system. In this overview, we focus on and discuss problems related to the different sources of biological material and sample handling, which are part of all preparatory and analytical steps. Straightforward protocols are desirable to avoid excessive purification steps, since loss of material at each step is inevitable. We would like to merge the two worlds of proteomics/peptidomics and neuroscience, and finally we consider different practical and technical aspects, illustrated with examples from our laboratory.
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| 50. |
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