| 1. |
- Lanemo Myhrinder, Anna, 1975-, et al.
(författare)
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A new perspective : molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:7, s. 3838-3848
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Tidskriftsartikel (refereegranskat)abstract
- The restricted immunoglobulin (Ig) repertoire found in B-cell chronic lymphocytic leukemia (CLL) implies a role for antigen(s) in the leukemogenesis. The nature of the antigens has, however, not been characterized, although examples of autoantigens have been demonstrated. We have analyzed a panel of 28 CLL cell lines and primary cultures, producing monoclonal Ig with different Ig heavy-chain variable region gene usage and mutational status, including several complementarity determining region 3 homology subset members. Using mass-spectrometry, immunoassays, or protein macroarrays, we have discovered novel antigens binding to CLL Igs. These antigens included cytoskeletal proteins vimentin, filamin B, and cofilin-1, but also phosphorylcholine-containing antigens (eg, Streptococcus pneumoniae polysaccharides and oxidized low-density lipoprotein [oxLDL]). Additional new antigens identified were cardiolipin and proline-rich acidic protein-1. Remarkably, these antigens represent molecular motifs exposed on apoptotic cells/blebs and bacteria, and several CLL Igs bound to apoptotic Jurkat cells. In conclusion, these intriguing data, showing a limited target structure recognition, indicate that CD5(+) CLL B cells are derived from a cell compartment that produces "natural antibodies," which may be instrumental in elimination and scavenging of apoptotic cells and pathogenic bacteria.
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| 2. |
- Myhrinder, Anna Lanemo, 1975-, et al.
(författare)
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Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:8, s. 1769-1779
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.
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| 3. |
- Rosén, Anders, et al.
(författare)
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Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.
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| 4. |
- Danielsson, Marie, et al.
(författare)
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Mini-seedlings of Picea abies are less attacked by Hylobius abietis than conventional ones : Is plant chemistry the explanation?
- 2008
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Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 23:4, s. 299-306
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Tidskriftsartikel (refereegranskat)abstract
- The pine weevil, Hylobius abietis (L.), is a major pest in conifer reforestation areas in the Palaearctic region. Size and chemistry of the seedlings may explain the damage rates in plantations. The performance of 10-week containerized seedlings (mini-seedlings) was compared with 1-year-old conventional seedlings of Norway spruce, Picea abies (L.), in a field experiment in central Sweden. After 2 years the weevil damage was lower for the mini-seedlings than for the conventional seedlings (3.5 vs 55%). After 3 years, the overall survival was 82 and 75%, respectively. Weevil damage was the main cause of mortality for conventional seedlings, whereas mini-seedlings mainly died from drought. Volatiles of the two seedling types were compared by solid-phase microextraction-gas chromatography -mass spectrometry (SPME-GC-MS). Unwounded mini-seedlings and conventional seedlings differed in their compositions of monoterpenes and sesquiterpenes. Miniseedlings mainly emitted limonene, known to be repellent to the pine weevil. When wounded, green leaf volatiles were released by mini-seedlings while the pine weevil attractant alpha-pinene was released by conventional seedlings. Volatiles may partly explain the mini-seedlings' resistance against weevil attack. Further studies are needed to clarify how long this miniseedling effect remains.
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| 5. |
- Engdahl, Johan, et al.
(författare)
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Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding : the AF SPICE protocol
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.Methods and analysis: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥ 70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.Ethics and dissemination: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454.
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| 6. |
- Georgoudaki, Anna-Maria, et al.
(författare)
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Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 15:9, s. 2000-2011
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming-TAM-populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, Fc gamma RIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment.
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| 7. |
- Gunnarsson, Cecilia, 1970-, et al.
(författare)
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17β-hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer
- 2005
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 92:3, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- The 17β-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P = 0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P = 0.0047), ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P = 0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.
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| 8. |
- Hagell, Peter, et al.
(författare)
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Apomorphine formulation influences subcutaneous complications in continuous apomorphine pump therapy for Parkinson’s disease
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To explore if the occurrence and severity of subcutaneous (sc) nodules is influenced by the pharmaceutical formulation of apomorphine used for sc infusion in advanced Parkinson’s disease (PD). Background: Apomorphine infusion is an effective therapy in advanced PD, but a limitation is troublesome sc nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal clinical experience has suggested that shifting from one of these (Apo-Go PumpFill; apoGPF) to another (Apomorphine PharmSwed; apoPS, developed in Sweden) may influence the occurrence and severity of sc nodules. Methods: In this multicenter open-label prospective observational study, 15 people with advanced PD (mean PD- duration, 13.4 years; median Hoehn & Yahr, IV) on apoGPF since a mean of 2.1 years and with troublesome sc nodules were switched to apoPS. Ongoing interventions to treat existing nodules (ultrasound, massage, Hirudoid cream) continued, and apomorphine as well as other drugs was managed accordingto clinical routines. Data were collected between May 2015 and March 2017; at baseline, at the time of switching (about 2 weeks later), and up to 1.7-4.2 (mean, 2.5) months post-switch follow-up. Primary outcomes were total nodule numbers, size (mm diameter for the 5 worst nodules), consistency (scored 0-3 for the 5 worst nodules), and associated skin changes (scored 0-4 for the 5 worst nodules) and pain (scored 0-5). Patients also rated their perceived PD severity and motor complications (UPDRS IV). Patient preferences 5-12 months post-switch (2-9 months after follow-up) were also recorded. Results: Apomorphine and L-dopa doses did not change over the observation period (P≥0.400). Baseline nodule numbers (7.4 vs. 4.6; P<0.003), size (92.9 vs. 54.1 mm; P=0.016), consistency (11 vs. 5; P=0.003), skin changes (3 vs. 1.5; P=0.205), and average pain (1 vs. 0; P=0.020) improved 11 weeks post-switch. Patient-reported PD severity (P=0.020) and motor fluctuations improved (P=0.051), whereas dyskinesias tended to increase (P=0.205). At 5-12 months post-switch, 13 patients had decided to remain on apoPS; mainly due to improved nodules. Conclusions: These observations suggest that apoPS may have a better safety profile compared to apoGPF in terms of sc nodule occurrence and severity. There is a need for larger, randomized controlled studies for firmer conclusions.
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| 9. |
- Hagell, Peter, et al.
(författare)
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Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
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Ingår i: Journal of Neurology. - : D. Steinkopff-Verlag. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
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Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
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| 10. |
- Hallgren, Karin, 1957-, et al.
(författare)
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Musik och politik i svenskt 1970-tal : musikspridning, jämlikhet och kommersialism på de kungliga teatrarna och SVT?
- 2017
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Ingår i: Musikforskning idag. - : Luleå University of Technology. ; , s. 26-27
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Under 1960- och 70-talen var debatten om kulturfrågor intensiv i Sverige. Beslutet om kulturpolitikens inriktning 1974 fick stor betydelse för kulturlivets organisering under de kommande decennierna. Den nya kulturpolitiken byggde bland annat på idéer om behovet av att sprida kultur jämlikt till alla invånare i Sverige, samt att ”Kulturpolitiken skall motverka kommersialismens negativa verkningar inom kulturområdet” (Kulturutredningen 1995:62). Samtidigt hade svenska grupper inom populärmusiken stora internationella framgångar, med ABBA som det mest framgångsrika och mest kända exemplet. Kulturdebatten blev polariserad, med tydliga motsättningar mellan förespråkare för kulturpolitikens grundläggande värderingar å ena sidan och ”den kommersiella musikens” företrädare å den andra.Denna motsättning är fokus för vår studie. Hur påverkades olika institutioner av den nya kulturpolitiken och av de aktuella idéerna i debatten? I denna studie görs en jämförelse mellan några konkreta yttringar inom musiklivet. Exempel ges från de traditionstyngda scenerna Kungliga Operan och Dramaten i Stockholm samt från SVT:s verksamhet, där programmet ”Alternativ festival” från 1975 används som en fallstudie. Förutom utvalda program och föreställningar bygger studien på arkivmaterial från institutionerna. Vi använder en komparativ metod och genomför föreställningsanalys utifrån teatervetenskapliga metoder.1970-talets kulturdebatt inom musikens område är till vissa delar beskriven och analyserad i tidigare forskning (se exv. Arvidsson 2008; Thyrén 2009) men en jämförelse mellan institutioner av detta slag har inte gjorts tidigare. Här finns en möjlighet att visa hur kulturlivet i stort påverkades av de nya idéerna och hur både hög- och lågutbildade gavs tillfälle att ta del av detta.
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