| 31. |
- Nilsson, Ulrika Nilsson, et al.
(författare)
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SPE and HPLC/UV of resin acids in colophonium-containing products.
- 2008
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Ingår i: Journal of separation science. - Weinheim, Fed. Rep. of Germany : Wiley. - 1615-9314 .- 1615-9306. ; 31:15, s. 2784-90
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Tidskriftsartikel (refereegranskat)abstract
- A new method, involving SPE and HPLC/UV diode-array detection (DAD), was developed for the quantification of colophonium components in different consumer products, such as cosmetics. Colophonium is a common cause of contact dermatitis since its components can oxidize into allergens on exposure to air. Three different resin acids were used as markers for native and oxidized colophonium, abietic acid (AbA), dehydroabietic acid (DeA), and 7-oxodehydroabietic acid (7-O-DeA). The SPE method, utilizing a mixed-mode hydrophobic and anion exchange retention mechanism, was shown to yield very clean extracts. The use of a urea-embedded C(12) HPLC stationary phase improved the separation of the resin acids compared to common C(18). Concentrations higher than 2 mg/g of both AbA and DeA were detected in wax strips. In this product also 7-O-DeA, a marker for oxidized colophonium, was detected at a level of 28 microg/g. The LODs were in the range of 7-19 microg/g and the LOQs 22-56 microg/g. The method is simple to use and can be applied on many types of technical products, not only cosmetics. For the first time, a method for technical products was developed, which separates AbA from pimaric acid.
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| 32. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 33. |
- Vinnars, Marie-Therese, et al.
(författare)
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Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
- 2018
-
Ingår i: American Journal of Reproductive Immunology. - : Wiley. - 1046-7408 .- 1600-0897. ; 80:1
-
Tidskriftsartikel (refereegranskat)abstract
- ProblemPre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta. Method of studyThe cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR. ResultsThe cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta. ConclusionThe destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
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| 34. |
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| 35. |
- Wicher, Grzegorz K., et al.
(författare)
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Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury
- 2017
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 34:22, s. 3173-3182
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.
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| 36. |
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| 37. |
- Ahlén, Gustaf, et al.
(författare)
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Mannosylated mucin-type immunoglobulin fusion proteins enhance antigen-specific antibody and T lymphocyte responses
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Targeting antigens to antigen-presenting cells (APC) improve their immunogenicity and capacity to induce Th1 responses and cytotoxic T lymphocytes (CTL). We have generated a mucin-type immunoglobulin fusion protein (PSGL-1/mIgG2b), which upon expression in the yeast Pichia pastoris became multivalently substituted with O-linked oligomannose structures and bound the macrophage mannose receptor (MMR) and dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) with high affinity in vitro. Here, its effects on the humoral and cellular anti-ovalbumin (OVA) responses in C57BL/6 mice are presented.OVA antibody class and subclass responses were determined by ELISA, the generation of anti-OVA CTLs was assessed in 51Cr release assays using in vitro-stimulated immune spleen cells from the different groups of mice as effector cells and OVA peptide-fed RMA-S cells as targets, and evaluation of the type of Th cell response was done by IFN-γ, IL-2, IL-4 and IL-5 ELISpot assays.Immunizations with the OVA − mannosylated PSGL-1/mIgG2b conjugate, especially when combined with the AbISCO®-100 adjuvant, lead to faster, stronger and broader (with regard to IgG subclass) OVA IgG responses, a stronger OVA-specific CTL response and stronger Th1 and Th2 responses than if OVA was used alone or together with AbISCO®-100. Also non-covalent mixing of mannosylated PSGL-1/mIgG2b, OVA and AbISCO®-100 lead to relatively stronger humoral and cellular responses. The O-glycan oligomannoses were necessary because PSGL-1/mIgG2b with mono- and disialyl core 1 structures did not have this effect.Mannosylated mucin-type fusion proteins can be used as versatile APC-targeting molecules for vaccines and as such enhance both humoral and cellular immune responses.
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| 38. |
- Ahlström, Monica, et al.
(författare)
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Ett praktiskt försök : nationell prioriteringsmodell tillämpad i Landstinget i Kalmar Län
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)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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| 39. |
- Ali, Ashfaq, et al.
(författare)
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Paranoid potato : phytophthora-resistant genotype shows constitutively activated defense
- 2012
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Ingår i: Plant Signaling and Behavior. - : Informa UK Limited. - 1559-2316 .- 1559-2324. ; 7:3, s. 400-408
-
Tidskriftsartikel (refereegranskat)abstract
- Phytophthora is the most devastating pathogen of dicot plants. There is a need for resistance sources with different modes of action to counteract the fast evolution of this pathogen. In order to better understand mechanisms of defense against P. infestans, we analyzed several clones of potato. Two of the genotypes tested, Sarpo Mira and SW93-1015, exhibited strong resistance against P. infestans in field trials, whole plant assays and detached leaf assays. The resistant genotypes developed different sizes of hypersensitive response (HR)-related lesions. HR lesions in SW93-1015 were restricted to very small areas, whereas those in Sarpo Mira were similar to those in Solanum demissum, the main source of classical resistance genes. SW93-1015 can be characterized as a cpr (constitutive expressor of PR genes) genotype without spontaneous microscopic or macroscopic HR lesions. This is indicated by constitutive hydrogen peroxide (H₂O₂) production and PR1 (pathogenesis-related protein 1) secretion. SW93-1015 is one of the first plants identified as having classical protein-based induced defense expressed constitutively without any obvious metabolic costs or spontaneous cell death lesions.
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| 40. |
- Almasoudi, Wejdan, et al.
(författare)
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Co-occurrence of CLCN2-related leukoencephalopathy and SPG56
- 2023
-
Ingår i: Clinical Parkinsonism and Related Disorders. - : Elsevier BV. - 2590-1125. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Family Report: Two rare autosomal recessive neurological disorders, leukoencephalopathy with ataxia and spastic paraplegia 56 (SPG56), were found in members of the same family. Two siblings presented with spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia; their consanguineous parents were unaffected. Ophthalmological examination revealed chorioretinopathy. Brain MRI showed T2 hyperintensities and T1 hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected siblings were homozygous for CYP2U1 c.947A > T p.(Asp316Val), a known cause for SPG56. However, they were also homozygous for the novel variant CLCN2 c.607G > T, p.(Gly203Cys), classified as a variant of unknown significance. Testing of additional family members revealed homozygosity for both variants in an additional brother, whom we initially considered unaffected. Both male CLCN2 carriers were infertile, and review of the literature revealed one reported case with azoospermia, however the brother had no overt signs of SPG56. His testicular biopsy revealed incomplete maturation arrest in spermatogenesis; clinically we found mild memory impairment and hand tremor and MRI showed similar changes as his siblings. We consider CLCN2 c.607G > T pathogenic because of the neuroradiological and clinical findings, including azoospermia. Conclusion: Considerable workup may be required to determine the pathogenicity of novel variants, and to unambiguously associate phenotype with genotype. In very rare disorders, highly specific clinical or biomarker combinations provide sufficient evidence for a variant's pathogenicity. Phenotypic variation of monogenic disorders described in the literature may be attributed to a second co-occurring monogenic disorder, especially in consanguineous families. SPG56 may have reduced penetrance.
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