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- Thulin, Åsa, et al.
(author)
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Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein
- 2009
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In: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 7:11, s. 1792-1802
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Journal article (peer-reviewed)abstract
- The angiogenesis inhibitor histidine-rich glycoprotein (HRG) constitutes one of several examples of molecules regulating both angiogenesis and hemostasis. The antiangiogenic properties of HRG are mediated via its proteolytically released histidine- and proline-rich (His/Pro-rich) domain.Using a combination of immunohistochemistry and massspectrometry, we here provide biochemical evidence for thepresence of a proteolytic peptide, corresponding to the antiangiogenic domain of HRG, in vivo in human tissue. This finding supports a role for HRG as an endogenous regulator of angiogenesis. Interestingly, the His/Pro-rich peptide bound to the vessel wall in tissue from cancer patients but not to the vasculature in tissue from healthy persons.Moreover, the His/Pro-rich peptide was found in close association with platelets. Relesate from in vitro–activated platelets promoted binding of the His/Pro-rich domain of HRG to endothelial cells, an effect mediated by Zn2+.Previous studies have shown that zinc-dependent bindingof the His/Pro-rich domain of HRG to heparan sulfate on endothelial cells is required for inhibition of angiogenesis.We describe a novel mechanism to increase the local concentration and activity of an angiogenesis inhibitor,which may reflect a host response to counteract angiogenesis during pathologic conditions. Our finding that tumor angiogenesis is elevated in HRG-deficient mice supports this conclusion.
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- Erlandsson, Anna, et al.
(author)
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Autocrine/Paracrine platelet-derived growth factor regulates proliferation of neural progenitor cells
- 2006
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 66:16, s. 8042-8048
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Journal article (peer-reviewed)abstract
- Growth factors play an important role in regulating neural stem cell proliferation and differentiation. This study shows that platelet-derived growth factor (PDGF) induces a partial differentiation of neural stem/progenitor cells (NSPCs) in the absence of other mitogens in vitro. NSPCs thus acquire an immature morphology and display markers for both neurons and glia. In addition, these cells do not readily mature in the absence of further stimuli. When NSPC cultures treated with PDGF were exposed to additional differentiation factors, however, the differentiation proceeded into neurons, astrocytes, and oligodendrocytes. We find that NSPC cultures are endowed with an endogenous PDGF-BB production. The PDGF-BB expression peaks during early differentiation and is present both in cell lysates and in conditioned medium, allowing for autocrine as well as paracrine signaling. When the NSPC-derived PDGF was inhibited, progenitor cell numbers decreased, showing that PDGF is involved in NSPC expansion. Addition of a PDGF receptor (PDGFR) inhibitor resulted in a more rapid differentiation. Neurons and oligodendrocytes appeared earlier and had more elaborate processes than in control cultures where endogenous PDGFR signaling was not blocked. Our observations point to PDGF as an inducer of partial differentiation of NSPC that also sustains progenitor cell division. Such an intermediate stage in stem cell differentiation is of relevance for the understanding of brain tumor development because autocrine PDGF stimulation is believed to drive malignant conversion of central nervous system progenitor cells.
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4. |
- Nilsson, Anna, 1974-
(author)
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Identification and Syntheses of Semiochemicals Affecting Mnesampela privata and Trioza apicalis
- 2009
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Licentiate thesis (other academic/artistic)abstract
- The Autumn gum moth, Mnesampela privata (Lepidoptera: Geometridae) is an endemic Australian moth whose larvae feed upon species of Eucalyptus. The moths favorite host plants are E. globulus and E. nitens which are the most important species used in commercial plantations of the Australian pulpwood industry. The autumn gum moth has become one of the most significant outbreak insects of eucalyptus plantations throughout Australia. As a consequence great financial losses to the forest industry occur. Today insecticides such as pyrethroids are used for control of eucalyptus defoliators as M. privata. The carrot psyllid, Trioza apicalis (Homoptera: Psylloidea), is one of the major pests of carrot (Daucus carota) in northern Europe. The psyllid causes curling of the carrot leafs and reduction of plant growth. Today the carrot crops are protected with the pyrethroid insecticide cypermethrin, which is toxic to aquatic organisms and is, from 2010, prohibited for use in Sweden by the Swedish Chemicals Inspectorate. An alternative to insecticides is to protect the seedlings with semiochemicals, a chemical substance or mixture of them that carries a message. This thesis describes the identification and the syntheses of semiochemicals from the above mentioned insect species. From analysis of abdominal tip extracts of M. privata females from Tasmania a blend of (3Z,6Z,9Z)-3,6,9-nonadecatriene and (3Z,6Z,9Z)-3,6,9-heneicosatriene was identified as the sex pheromone of this species. The identification of the C19- and C21-trienes was confirmed by synthesis. In the analysis of carrot leaf extracts we found a compound, α-cis-bergamotene, that induces antennal response in the carrot psyllid. This is just the beginning of the studies of trying to manipulate this psyllid with semiochemicals instead of insecticides.
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6. |
- Nilsson-Ardnor, Sofie, et al.
(author)
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Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.
- 2005
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In: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1666-1671
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden. METHODS: A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of PDE4D to stroke. RESULTS: Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06; P=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in PDE4D (odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in PDE4D. CONCLUSIONS: Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the PDE4D gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.
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7. |
- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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8. |
- Welin, Anna-Karin, 1965, et al.
(author)
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White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.
- 2005
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In: Pediatric research. - 0031-3998. ; 58:1, s. 100-5
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Journal article (peer-reviewed)abstract
- Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.
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9. |
- Ahlström, Monica, et al.
(author)
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Ett praktiskt försök : nationell prioriteringsmodell tillämpad i Landstinget i Kalmar Län
- 2008
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Reports (other academic/artistic)abstract
- Idag finns en nationell modell för hur öppna vertikala prioriteringar kan genomföras. Den är resultatet av de samlade erfarenheterna av att omsätta riksdagens riktlinjer för prioriteringar i praktiskt prioriteringsarbete. Modellen är framtagen av Socialstyrelsen, PrioriteringsCentrum samt flera vårdförbund och landsting gemensamt. Också FSA och LSR har ställt sig bakom den. Fram tills nu har det dock saknats praktisk erfarenhet av att tillämpa modellen inom arbetsterapi och sjukgymnastik. Men sedan drygt två år tillbaka har de båda rehabiliteringsenheterna Samrehab och Rehab Söder i Landstinget i Kalmar län med stöd av PrioriteringsCentrum bedrivit ett prioriteringsarbete i enlighet med modellen. Det är deras erfarenheter denna rapport handlar om.Prioriteringsarbetet har med nära stöd av verksamhetsledningarna letts av en projektgrupp bestående av arbetsterapeuter och sjukgymnaster från de båda enheterna som fungerat som handledare, ansvarat för metodutveckling och utbildning samt kontinuerligt utvärderat arbetet. Själva tillämpningen av den nationella modellen har ett antal utvecklingsgrupper inom olika specialistområden stått för. De har valt ut och rangordnat tillstånd och olika åtgärder som de ansett angelägna att ta fram prioriteringar för.Ett av syftena med prioriteringsarbetet i Samrehab och Rehab Söder var att få till stånd länsövergripande prioriteringar inom vissa verksamheter och/eller för vissa sjukdomstillstånd för en mer likvärdig vård. Idag finns elva sådana prioriteringsordningar presenterade på landstingets intranät och ytterligare ett tiotal är under bearbetning. Utöver vinsterna med det förbättrade samarbetet mellan länsdelarna har alltså den interna öppenheten i prioriteringarna ökat. Alla anställda kan lätt få fram prioriteringsordningarna via basenheternas hemsidor när man behöver det. Andra vinster av prioriteringsarbetet är att kännedomen och kunskapen om riksdagens riktlinjer för prioriteringar har ökat, att en större del av basenheternas verksamhet idag är faktabaserad än innan prioriteringsarbetet startade samt att den kliniska erfarenheten har tillvaratagits och dokumenterats på ett mer systematiskt sätt än tidigare. Det har dessutom skett en utveckling av den nationella modellen som har blivit mer konkret vad det gäller svårighetsgrad och nytta. En majoritet av deltagarna i utvecklingsgrupperna har haft en positiv inställning till att arbeta med prioriteringar utifrån modellen och upplever också att de erhållit ett språk som gör det möjligt att kommunicera prioriteringar med politiker och landstingsledning.I rapporten presenteras också de frågor kring modellens olika steg som dykt upp under arbetets gång. Tre frågor har dominerat; syftet med prioriteringsarbetet, tolkningen av modellen samt dokumentationen av prioriteringsarbetet. Syftet har inte alltid upplevts som helt klart och sambandet mellan prioriteringsarbetet och annat kvalitetsarbete som t ex framtagande av behandlingsriktlinjer har varit otydligt. När det gäller tolkningen av modellen har t ex graderingen av svårighetsgrad och patientnytta gett upphov till frustration. Också den skriftliga presentationen av prioriteringsordningarna har stundtals upplevts som krånglig och svår att förmedla till övriga medarbetare på ett användbart sätt.Alla de åtgärder som projektgruppen vidtagit för att underlätta de svårigheter som dykt upp delar de här med sig av i rapporten. Likaså pekar de ut viktiga förutsättningar för ett prioriteringsarbete (som t ex tid, kompetens, kontinuitet och legitima deltagare). Syftet med att pröva om den nationella modellen för öppna vertikala prioriteringar är användbar i Samrehabs och Rehab Söders prioriteringsarbete är uppnådd och det har inte framkommit något som ger anledning att ifrågasätta modellens grundstruktur. Förslag har dock givits bl a avseende bedömning av svårighetsgrad och patientnytta för att ytterligare underlätta tillämpningen.Nu planerar enheterna att gå vidare med sitt prioriteringsarbete, dels genom att fortsätta att ta fram behandlingsriktlinjer som kombineras med prioriteringar men också genom att ytterligare utveckla prioriteringsstödet för de enskilda medarbetarna i deras dagliga patientarbete. Om andra verksamheter i Sverige följer efter detta exempel från Kalmar län med att öppet redovisa hur de hanterar prioriteringar i sin verksamhet kommer ytterligare nya erfarenheter att hjälpa metodutvecklingen på traven.
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