| 1. |
- Lavasani, Shahram, et al.
(author)
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Abnormal DNA damage-inducible protein in cells from Sjogren's syndrome patients
- 1998
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 11:4, s. 363-369
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Journal article (peer-reviewed)abstract
- Antinuclear antibodies are commonly found in patients with Sjogren's syndrome. It has been suggested that the development of antinuclear antibodies depends on the activation of the spliceosome and other transcription-related subcellular particles, some of which have recently been shown also to function in DNA-modifying processes, such as DNA repair and V(D)J recombination. These observations add weight to a previously proposed model for the aetiology of Sjogren's syndrome. This includes the abnormal processing of the T-cell receptor and immunoglobulin genes. To test this hypothesis further, the present study on DNA-modifying proteins in Sjogren's syndrome was initiated. Gel-shift experiments using protein extracted from UV-treated Sjogren cells provided evidence of high molecular weight DNA-binding protein in six out of 12 Sjogren patients studied (but not among seven healthy controls). Some Sjogren sera displayed antibodies to protein extracts from cells treated with psoralen plus UVA radiation. These results indicate an abnormal DNA damage-inducible response in Sjogren's syndrome. It may therefore be concluded that alterations in nuclear protein may play a role in the aetiology of Sjogren's syndrome.
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| 2. |
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| 3. |
- Appelberg, Kajsa, et al.
(author)
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Cost-Effectiveness of Newborn Screening for Phenylketonuria and Congenital Hypothyroidism
- 2023
-
In: The Journal of Pediatrics. - : MOSBY-ELSEVIER. - 0022-3476 .- 1097-6833. ; 256, s. 38-43.e3
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Journal article (peer-reviewed)abstract
- Objective To evaluate the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism compared with no screening. Study design A decision-analytic model was developed to estimate and compare the long-term (80 years) costs and health effects of newborn screening for PKU and congenital hypothyroidism. Data were obtained from the liter-ature and translated to Swedish conditions. A societal perspective was taken, including costs falling on health care providers, municipal care and services, as well as production loss due to morbidity. Results Screening 100 000 newborns for PKU resulted in 73 gained quality-adjusted life-years (QALYs) compared with no screening. When adding congenital hypothyroidism, the number of gained QALYs was 232 compared with PKU alone, adding up to a total of 305 QALYs gained. Corresponding cost estimates were $80.8, $70.3, and $10.05 million USD for no screening, PKU screening, and PKU plus congenital hypothyroidism screening, respectively, indicating that screening for PKU plus congenital hypothyroidism was more effective and less costly compared with the other strategies. The majority of cost savings with PKU plus congenital hypothyroidism screening was due to reductions in productivity losses and municipal care and services costs. Conclusion The Swedish newborn screening program for PKU and congenital hypothyroidism saves substantial costs for society while generating additional QALYs, emphasizing the importance of public investments in early diagnosis and treatment. (J Pediatr 2023;256:38-43).
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| 4. |
- Arnfalk, Peter, et al.
(author)
-
Miljöarbete inom Svensk Tillverkningsindustri. En färd från myt till verklighet
- 2008
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Reports (other academic/artistic)abstract
- Föreliggande undersökning genomfördes under hösten och vintern 2007 av forskare vid Internatio-nella Institutet för Industriell Miljöekonomi (IIIEE) vid Lunds Universitet på uppdrag av Miljömålsrå-det. Syftet med undersökningen var att belysa dagens miljöarbete inom tillverkningsindustrin och göra jämförelser med resultat från tidigare motsvarande studier som genomfördes 1991 och 1998. Syftet var också att belysa hur och i vilken omfattning de nationella miljökvalitetsmålen påverkar företagens miljöarbete. Rapporten bidrog därmed till den samlade utvärderingen av arbetet med de nationella miljökvalitetsmålen som presenterades under våren 2008. Undersökningen baserades på telefonintervjuer med miljöansvariga/personer som konkret utför miljöarbete i 272 slumpvis valda tillverkande företag fördelade över landet i olika branscher och storleksklasser. Bortfallsfrekvensen var 16 procent. Miljöarbetet undersöktes genom vilka konkreta åtgärder som genomförts inom olika områden, hur dessa åtgärder speglas i den övergripande bil-den av företagets miljöaspekter, hur miljöarbetet organiserats och personalen involverats. En sam-lad bedömning av företagens miljöarbete gjordes genom att indela dem i olika kategorier. Katego-rierna motsvarar en femgradig ”betygsskala” från miljöpassiva till miljöanpassade strategier för mil-jöarbetet. Företagens drivkrafter, policies och motiv för miljöarbete undersöktes också. Under tidsperioden 1991- 2007 har tillverknings¬industrins miljöarbete suc¬cessivt förbättrats. Kategorimedelvärdet (”medel¬betyget”) har höjts mellan varje undersökningstillfälle, såväl totalt sett som inom varje storleksklass, vilket framgår av diagrammet. Kategorimedel¬värdet för hela till-verkningsindustrin var år 2007 1,9 jämförelse med 1,4 år 1991. Kategorimedelvärdet för anställda inom tillverkningsindustrin har ökat från 2,1 år 1991 till 2,7 år 2007. Ett mönster som går igen från de tidigare undersökningarna är att de större företagen i allmänhet har mer utvecklat miljöarbete och tydligare miljöstrategi än de mindre företagen. De största företagen (>500 anställda) införde mycket av sitt miljöarbete under 1990-talet och har fortsatt att utveckla sitt miljöarbete. Det är dock bland de medelstora (50 – 499 anställda) företagen de tydligaste förbättringarna kan konstateras. Kategorimedelvärdet har även ökat inom storleksklassen småföretag (1- 49 anställda), men i väsentligt lägre utsträckning. Fortfarande är miljömedvetenheten relativt låg bland de minsta före-tagen. Miljökravställarna har skiftat från att domineras av miljömyndigheterna till i allt högre grad utgöras av kunder och konsumenter. Klassiska ”end-of-pipe”-lösningar på miljöproblemen har under perio-den 1991-2007 kompletterats en blandning av tekniska och organisatoriska åtgärder. Miljöanpass-ning av transporterna har seglat upp som en miljöaspekt som anses som allt viktigare och underle-verantörernas roll i miljöarbetet har fått större betydelse. Miljöarbetet integreras i styrningen och uppföljningen i företagen och ifrågasätts alltmer sällan. Företag med miljöledningssystem (ISO 14001) har generellt ett mer utvecklat och systematiskt miljöarbete. De flesta tillverkningsföretag (78 procent) känner inte till Sveriges 16 miljökvalitetsmål. Omkring var femte företag (21 procent) känner till målen, men endast 1 procent av företagen vet vilka de olika målen är. Dessa siffror präglas dock av småföretagens stora dominans i antal. Mer än hälften av de företag som har femtio eller fler anställda känner till miljökvalitetsmålen. Det är endast 5 procent av det totala antalet tillverkande företag som anser sig påverkade av miljömålen. Eftersom dessa i huvudsak är större företag sysselsätter de emellertid ca 30 procent av arbetskraften inom tillverk-ningsindustrin.
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| 5. |
- Bredberg, Anders, et al.
(author)
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A role of the macrophage in Sjogen's syndrome?
- 2003
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 32:4, s. 255-255
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Journal article (other academic/artistic)
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| 6. |
- Bredberg, Anders, et al.
(author)
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Recent findings shed light on the aetiopathogenesis of Sjogren's syndrome
- 2005
-
In: Aktuelle Rheumatologie. - : Georg Thieme Verlag KG. - 0341-051X .- 1438-9940. ; 30:1, s. 23-26
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Journal article (peer-reviewed)abstract
- The systemic clinical picture of SS patients can be traced back to a disposition of many cell types to over-react when confronted with stress stimuli. This will influence basic cellular processes such as apoptosis and acetylcholine receptor signaling. This tissue hyper-reactivity may also explain the observed autoimmune features, and may constitute a major aetiopathogenetic determinant in SS.
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| 7. |
- Bredberg, Anders, et al.
(author)
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Sjogren's syndrome and the danger model.
- 2005
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 44:8, s. 965-970
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Research review (peer-reviewed)
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| 8. |
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| 9. |
- Bugaytsova, Jeanna, et al.
(author)
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pH regulated H. pylori adherence : implications for persistent infection and disease
-
Other publication (other academic/artistic)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 10. |
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| 11. |
- Faraz, Mahmood, 1978-
(author)
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Investigations of Leucine-rich repeats and immunoglobulin-like domain-proteins 1 and 2 (LRIG1 and LRIG2) and their genes in cancer
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- The mammalian leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family consists of three different members, LRIG1, LRIG2, and LRIG3. These genes are expressed in all human and mouse tissues analyzed to date. All LRIG proteins share similar and evolutionary conserved structural domains including a leucine-rich repeat domain, three immunoglobulin-like domains, a transmembrane domain, and a cytosolic tail. Since the discovery of this family, around 20 years ago, various research groups have shown the importance of this family in cancer biology and prognosis. The aim of this thesis was to further investigate the role of LRIG1 and LRIG2 in cancer.To investigate the roles of LRIG1 and LRIG2 in physiology and gliomagenesis, we generated Lrig1- and Lrig2-deficient mice and induced platelet-derived growth factor B (PDGFB)-driven gliomagenesis. We studied the effects of Lrig2 ablation on mouse development and survival and investigated if the ablation of Lrig1 or Lrig2 affects the incidence or malignancy of induced gliomas. We also investigated if Lrig2 ablation affects Pdgfr signaling in mouse embryonic fibroblasts (MEFs). Additionally, we analyzed the effects of ectopic LRIG1 expression in human primary glioblastoma cell lines TB101 and TB107, in vivo and in vitro. We reported no macroscopic anatomical defect but reduced growth and increased spontaneous mortality rate in Lrig2-deficient mice. However, the Lrig2-deficient mice were protected against the induced gliomagenesis. Lrig2-deficient MEFs showed faster kinetics of induction of immediate-early genes in response to PDGFB stimulation, whereas the phosphorylations of Pdgfra, Pdgfrb, Erk1/2, and Akt1 appeared unaltered. Lrig1-heterozygote mice showed a higher incidence of high-grade tumors (grade IV) compared to wildtype mice, demonstrating a haploinsufficient function of Lrig1. LRIG1 overexpression suppressed TB107 cell invasion in vivo and in vitro, which was partially mediated through the suppression of the MET receptor tyrosine kinase.To identify LRIG1-interacting proteins, we used the yeast-two hybrid system and data-mined the Bio-Plex network of high throughput protein-protein interaction database. To study the function of interactors, we used a triple co-transfection system to overexpress LRIG1 and PDGFRA and downregulate endogenous levels of interactors by short hairpin RNAs (shRNAs), simultaneously. This analysis demonstrated that CNPY3, CNPY4, GAL3ST1, GML, HLA-DRA, LRIG2, LRIG3, LRRC40, PON2, RAB4A, and ZBTB16 were important for the PDGFRA-downregulating function of LRIG1.To investigate the clinical significance of LRIG1 copy number alterations (CNAs) in breast cancer, we used droplet digital PCR (ddPCR) to analyze 423 breast cancer tumors. We found that LRIG1 CNAs were significantly different in steroid-receptor-positive vs steroid-receptor-negative tumors and in ERBB2-amplified vs ERBB2-non-amplified tumors. In the whole cohort, patients with LRIG1 loss or gain had a worse metastasis-free survival than patients with normal LRIG1 copy numbers, however, among the early-stage breast cancer subgroup, this difference was not significant. In summary, Lrig1 behaved like a haploinsufficient tumor suppressor gene in malignant glioma, whereas Lrig2 appeared to promote malignant glioma. Our functional analysis of LRIG1 interactome uncovered several unanticipated and novel proteins that might be important for the regulation of receptor tyrosine kinases by LRIG1. LRIG1 CNAs predicted metastasis-free survival time in breast cancer. Hopefully, our findings might lead to a better understanding of the regulation of growth factor signaling and its importance in cancer biology and prognosis.
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| 12. |
- Gratzer, Karl, et al.
(author)
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Otto Steiger
- 2008
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In: Svenska Dagbladet 2008-04-08.
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Journal article (pop. science, debate, etc.)
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| 13. |
- Hagström, Hannes, et al.
(author)
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Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls
- 2020
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In: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 18:7, s. 1592-
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P <.001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P <.001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.
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| 14. |
- Henriksson, Dan, et al.
(author)
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Observer-Based Impedance Control in Robotics
- 2001. - 6
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In: IFAC Proceedings Volumes. ; 34, s. 369-374
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Conference paper (peer-reviewed)abstract
- This paper presents theoretical and experimental results on observer-based impedance control. Impedance control is a technique for robot force control, which is often used to deal with geometric uncertainty. The aim of this technique is to obtain a dynamic relation between position and force in interaction similar to Newton's second law. Here the velocity is used to modify the damping of the impedance relation. Since the velocity is not measurable, which is often the case for industrial robots, an observer is designed to reconstruct it. A good model of the robot joint used is obtained by system identification. Results on observer-based SPR feedback are applied in the design, and the stability issue is approached by a modified Popov criterion. The experiments are carried out on an ABB industrial robot 2000 at the Department of Automatic Control in Lund, Sweden.
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| 15. |
- Henriksson, Gunnel, et al.
(author)
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Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren's syndrome cells.
- 2002
-
In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 32:6, s. 458-465
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Journal article (peer-reviewed)abstract
- BackgroundCells from primary Sjögren's syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA-dependent protein kinase (DNA-PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell-cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS. DesignDNA-dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma-irradiated long-term T lymphocyte cultures. Cell-cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry. ResultsNo significant differences in the DNA-PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS-A and La/SS-B autoantibodies showed enhancement of both p53 peptide phosphorylation (P = 0·036) and G1 cell-cycle arrest (P = 0·015) in response to gamma radiation. ConclusionsSjögren's syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.
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| 16. |
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| 17. |
- Koch, Daniel, 1976-
(author)
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Structuring Fashion : Department Stores as Situating Spatial Practice
- 2007
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Doctoral thesis (other academic/artistic)abstract
- This dissertation investigates department stores as complex spatial and cultural buildings, in which values and ideas are expressed, negotiated, and produced. Situated in a cultural context commonly referred to as a society of consumption, where identity and social structures are worked out through consumption rather than production, the query turns to a specific act of consumption: that of shopping. More precisely, it investigates the role of space and spatial distribution in shopping. How space is distributed, arranged, or ordered allows for different possibilities in constructing categories from which the shoppers are to make a selection, and for how these categories can be related to one another, which informs the shoppers what belongs together, what is to be held apart, what is important, what is private, what is public, and what is of higher or lower status. It further supports, prevents, and promotes different routes and choices, giving different patterns of presence, publicity, privacy, purpose, etc. that not only affects the atmosphere of the spaces, but makes suggestions of what is found in them. These questions are investigated through a series of conceptual laboratories, each addressing the problem from different standpoints and focusing on different parts of the question: from how categories are constructed and given character, to how they form systems of values, how shoppers are trained in aesthetics of fashion, how relative degrees of presences are made use of, and how they appear influenced by spatial distribution. In this, the work shifts between qualitative and quantitative methods, each completing and evolving the other. It shows that to a remarkable degree, much of the emergent values and ideas can be understood through the filter of spatial configurations, and especially when treated as two systems: one of exposure and one of availability. As similar operations also affect patterns of movement and being, which enables them to also be related to publicity, privacy, and other social characters, the department stores can be understood as not only commercial spaces but as sites of negotiation of public culture. As such, both the analytic model and the more specific findings have important implications for architectural theory in general.
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| 18. |
- Larsson, Åke, et al.
(author)
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Immunohistochemistry of the B-cell Component in Lower Lip Salivary Glands of Sjögren's Syndrome and Healthy Subjects
- 2005
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:1, s. 98-107
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Journal article (other academic/artistic)abstract
- Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.
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| 19. |
- Larsson, Å., et al.
(author)
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Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren's syndrome subjects: Lack of correlation with apoptosis
- 2001
-
In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 54:3, s. 328-334
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Journal article (peer-reviewed)abstract
- The aim was to examine tissue expression of Ku protein in lower lip salivary gland (LSG) biopsies from cases of primary Sjogren's syndrome (SS) and from normal subjects. Methods: immunohistochemistry was used with antibodies to Ku70/86 and also Ki67, PCNA and p53. In addition, the Klenow method was applied in order to detect evidence of apoptosis. Sections of hyperplastic tonsil served as additional controls. Results: in normal controls, LSG acinar cells stained negatively whereas LSG excretory duct cell nuclei stained positively with Ku and Klenow and occasionally with PCNA but negatively with Ki67 and p53. In LSG focal sialadenitis of SS cases, some lymphocytic cells showed staining with Ku, Ki67, PCNA, Klenow and p53. In addition to duct cell Ku and Klenow as well as PCNA staining which was not much different from normals, a few ductal epithelial and also mononuclear cells stained with p53. In focal sialadenitis, some acinar cells showed staining with PCNA as well as with Klenow. Conclusions: our findings in LSG biopsies of SS cases added little to an increased understanding about the pathogenetic mechanisms in the development of focal sialadenitis in SS. However. in normal LSG. ductal epithelial but not acinar cells seem to express a constitutively specific Ku protein and Klenow profile, suggestive of DNA strand breaks but not clearly associated with ongoing apoptotic events. It may reflect an enhanced stress response, which may be pathogenetically important in the early events of focal sialadenitis development in primary Sjogren's syndrome.
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| 20. |
- Lindhagen, Elin, et al.
(author)
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Significant cytotoxic activity in vitro of the EGFR tyrosine kinase inhibitor gefitinib in acute myeloblastic leukaemia.
- 2008
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In: Eur J Haematol. - : Wiley. - 1600-0609 .- 0902-4441. ; 81:5, s. 344-353
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Journal article (peer-reviewed)abstract
- OBJECTIVES:Gefitinib inhibits epidermal growth factor receptor (EGFR) signalling, but may also act by non-EGFR dependent mechanisms. We have investigated the activity of gefitinib in haematological tumour cells, in particular acute myeloblastic leukaemia (AML).METHODS:Cytotoxic activity of gefitinib, alone or in combination with standard anti-leukaemic drugs, was assessed by the short-term fluorometric microculture cytotoxicity assay in tumour cells from 117 patients representing five haematological and five non-haematological malignancies. In AML, the EGFR status was analysed by immunochemistry. Gefitinib-induced apoptosis was investigated in a subset of AML samples, as well as in the leukaemia cell line MV-4-11, using a multiparametric high content screening assay. To confirm activation of caspase-3 in cells treated with gefitinib, a blocking test was carried out in which MV4-11 cells were pretreated with the specific caspase inhibitor DEVD-FMK.RESULTS:Gefitinib showed highest cytotoxic activity in AML (n = 19) with many samples being sensitive at concentrations achievable in clinical practice (<10 microM), and no difference between previously untreated and relapsed patients. No correlation between the activity of gefitinib and standard antileukaemic drugs (cytarabine, doxorubicin, etoposide) was observed. Combining gefitinib with these drugs resulted in mainly additive or synergistic (etoposide) effects, with no evidence of sequence dependency. The AML cells did not express the EGFR. Gefitinib induced apoptosis, which was at least partly mediated by activation of the caspase-3 pathway.CONCLUSION:In vitro, gefitinib has significant cytotoxic activity in AML by inducing apoptosis through non-EGFR dependent pathways.
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| 21. |
- Lindqvist, C Mårten, et al.
(author)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Journal article (peer-reviewed)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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| 22. |
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| 23. |
- Melcher, Ulrica, et al.
(author)
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Maintaining everyday life in a family with a dying parent : Teenagers' experiences of adapting to responsibility
- 2015
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In: Palliative & Supportive Care. - 1478-9515 .- 1478-9523. ; 13:6, s. 1595-1601
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Teenagers are living through a turbulent period in their development, when they are breaking away from the family to form their own identities, and so they are particularly vulnerable to the stressful situation of having a parent affected by a progressive and incurable illness. The current study sought to gain more knowledge about the ways that teenagers themselves describe living in a family with a seriously ill and dying parent. More specifically, the aims were to describe how teenagers are emotionally affected by everyday life in a family with a dying parent and to determine how they attempt to adapt to this situation.METHOD: The study employed a descriptive and interpretive design using qualitative content analysis. A total of 10 teenagers (aged 14-19 years, 7 boys and 3 girls) participated through repeated, individual, informal interviews that were carried out as free-ranging conversations.RESULTS: While contending with their own vulnerable developmental period of life, the teenagers were greatly affected by their parent's illness and took on great responsibility for supporting their parents and siblings, and for maintaining family life. Lacking sufficient information and support left them rather unprepared, having to guess and to interpret the vague signs of failing health on their own, with feelings of uncertainty and loneliness as a consequence.SIGNIFICANCE OF RESULTS: Support from healthcare professionals should be designed to help and encourage parents to have open communications about their illness with their teenaged children. Our results add further support to the literature, reinforcing the need for an approach that uses a systemic perspective and considers the family to be the appropriate unit of care and offers a suitable support system.
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| 24. |
- Melcher, Ulrica, et al.
(author)
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Teenagers with a Dying Parent : A Qualitative Retrospective Study
- 2014
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In: Abstracts of the 8th World Research Congress of the European Association for Palliative Care (EAPC) Lleida, Spain 5–7 June 2014. - : SAGE Publications. ; , s. 797-797
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Conference paper (other academic/artistic)abstract
- Background: Beeing a teenager living with a dying parent is well known to be distressing with a significant impact on teenagers psychological well-beeing. To support teenagers and prevent long-term psychological consequences we need to find out more about teenagers experiences. Aim: The aim was to explore teenagers experiences from living with a severely ill dying parent. Method: Repeated qualitative interviews were conducted with ten teenagers that had lost a parent within a year. The parent had received specialist palliative care by the time of death. Qualitative content analyses were used for analyses. Results: Preliminary results show that teenagers carry a great responsibility in the care of the sick parent and the healthy parent, siblings and general ordinary family matters. While carrying this responsibility they experience loneliness and try to adjust to the situation in different ways by being loyal to their parents. In their process to understand that the parent is dying they prepare by observing and trying to make sense of the illness symptoms they notice. Feeling trust to and support from the parents makes them feel more involved and less lonely and responsible. Conclusion: This study contributed with knowledge about great feelings of responsibility and loneliness among teenagers who has a dying parent. Healthcare professionals in palliative care could work to acknowledge and try to support the teenagers to feel involved, less lonely and less burdened by responsibility. An important aspect is also to support the healthy parent enough and thereby reduce the responsibility from the teenager.
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| 25. |
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| 26. |
- Sjöberg, Susanne, et al.
(author)
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Microbe-Mediated Mn Oxidation - A Proposed Model of Mineral Formation
- 2021
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In: Minerals. - : MDPI. - 2075-163X. ; 11:10
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Journal article (peer-reviewed)abstract
- Manganese oxides occur in a wide range of environmental settings either as coatings on rocks, sediment, and soil particles, or as discrete grains. Although the production of biologically mediated Mn oxides is well established, relatively little is known about microbial-specific strategies for utilizing Mn in the environment and how these affect the morphology, structure, and chemistry of associated mineralizations. Defining such strategies and characterizing the associated mineral properties would contribute to a better understanding of their impact on the local environment and possibly facilitate evaluation of biogenicity in recent and past Mn accumulations. Here, we supplement field data from a Mn rock wall deposit in the Ytterby mine, Sweden, with data retrieved from culturing Mn oxidizers isolated from this site. Microscopic and spectroscopic techniques are used to characterize field site products and Mn precipitates generated by four isolated bacteria (Hydrogenophaga sp., Pedobacter sp., Rhizobium sp., and Nevskia sp.) and one fungal-bacterial co-culture (Cladosporium sp.-Hydrogenophaga sp. Rhizobium sp.-Nevskia sp.). Two of the isolates (Pedobacter sp. and Nevskia sp.) are previously unknown Mn oxidizers. At the field site, the onset of Mn oxide mineralization typically occurs in areas associated with globular wad-like particles and microbial traces. The particles serve as building blocks in the majority of the microstructures, either forming the base for further growth into laminated dendrites-botryoids or added as components to an existing structure. The most common nanoscale structures are networks of Mn oxide sheets structurally related to birnessite. The sheets are typically constructed of very few layers and elongated along the octahedral chains. In places, the sheets bend and curl under to give a scroll-like appearance. Culturing experiments show that growth conditions (biofilm or planktonic) affect the ability to oxidize Mn and that taxonomic affiliation influences crystallite size, structure, and average oxidation state as well as the onset location of Mn precipitation.
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| 27. |
- Sjöberg, Susanne, 1969-, et al.
(author)
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Mn oxide precipitation by epilithic biofilms in the Ytterby mine, Sweden : formation of an YREE-enriched birnessite
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Other publication (other academic/artistic)abstract
- Biofilms scavenge and bind reduced Mn(II) as well as stabilize highly reactive Mn(III), favouring formation of Mn oxides. Mn oxidation and precipitation involve closely connected and concomitant abiotic and biotic biogeochemical mechanisms, often making the biogenicity of the mineral product difficult to determine. In order to use these precipitates as potential biosignatures, profound knowledge of the formation pathways is required. Here we have access to an underground Mn oxide producing ecosystem in which epilithic biofilms precipitate yttrium and rare earth element enriched birnessite-type Mn oxides. Microbial community composition combined with elemental data is investigated to provide insight into how different subsystems of this ecosystem (fracture water, Mn oxide producing biofilm, and bubble biofilm) interact with each other to form the birnessite. We find that the microbial assembly of the feeding water has little impact on the derived biofilms, in which the signature microbial groups rather results from water chemistry and environmental conditions. In the Mn oxide producing biofilm, bacteria are adapted to the emerging extreme environment (low temperature, no light, high metal concentration) which is generated by the biofilm itself. Microstructural characterizations show that the birnessite has a dendritic/shrublike or spherulitic/botryoidal growth pattern. Nucleation occurs in close association to the biofilm and Mn encrustations of cells and other organic structures serve as stable nuclei for further growth. The influence of organics decrease in importance as precipitates grow. In more evolved crystals, a repetitive pattern, Liesegang-type of rings, implies that abiotic factors dominate. Grown on a solid substrate, four bacterial (Hydrogenophaga sp., Pedobacter sp., Rhizobium sp. and Nevskia sp.) and one fungal species (Cladosporium sp.) are involved in Mn oxide production. Hydrogenophaga and Pedobacter oxidize Mn independently while Rhizobium needs a synergistic relationship with selected species (e.g., Nevskia). Members of the Pedobacter and Nevskia genera are previously not known Mn oxidizers. The onset of Mn precipitaiton takes place at different locations with respect to the cells for the different species. Precipitates are located intracellularly (possibly post mortem), on the bacterial cell walls, at the outer edges of more well developed crystals, within the extracellular organic matter (EOM) and on hyphal surfaces.
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| 28. |
- Theander, Elke, et al.
(author)
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Lymphoma and other malignancies in primary sjogren's syndrome A cohort study on cancer incidence and lymphoma predictors.
- 2006
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 65:Nov 10, s. 796-803
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Journal article (peer-reviewed)abstract
- Objectives: To assess the risk of lymphoproliferative disease or other malignancy (standardised incidence ratios (SIRs)), in patients with primary Sjogren's syndrome according to the American-European Consensus Criteria (AECC), compared with patients with sicca syndrome (non-AECC) and the background population. To identify predictors of malignancy and describe lymphoma types and survival probabilities. Methods: A linked register study using information from the Malmo "Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for calculation of SIRs was carried out. Detected lymphomas were reclassified according to the WHO classification. Cox regression analysis was used to study the predictive value of clinical, laboratory, and histological findings at the time of diagnosis. Results: 507 patients with a median follow up of 8 years (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI)) for malignancies in total and for non-Hodgkin's lymphomas (NHL) were 1.42 (0.98 to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was 0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18, 95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell ratio <= 0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse large B cell lymphomas. Conclusion: A 16-fold increased risk for development of NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for developing lymphoma.
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| 29. |
- Åberg, Anna, et al.
(author)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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In: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Journal article (peer-reviewed)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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