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- Broeren, Jurgen, et al.
(author)
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Neglect assessment as an application of virtual reality.
- 2007
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In: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 116:3, s. 157-63
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Journal article (peer-reviewed)abstract
- OBJECTIVE: In this study a cancellation task in a virtual environment was applied to describe the pattern of search and the kinematics of hand movements in eight patients with right hemisphere stroke. METHODS: Four of these patients had visual neglect and four had recovered clinically from initial symptoms of neglect. The performance of the patients was compared with that of a control group consisting of eight subjects with no history of neurological deficits. RESULTS: Patients with neglect as well as patients clinically recovered from neglect showed aberrant search performance in the virtual reality (VR) task, such as mixed search pattern, repeated target pressures and deviating hand movements. The results indicate that in patients with a right hemispheric stroke, this VR application can provide an additional tool for assessment that can identify small variations otherwise not detectable with standard paper-and-pencil tests. CONCLUSION: VR technology seems to be well suited for the assessment of visually guided manual exploration in space.
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4. |
- Broeren, Jurgen, et al.
(author)
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Virtual rehabilitation after stroke.
- 2008
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In: Studies in health technology and informatics. - 0926-9630 .- 1879-8365. ; 136, s. 77-82
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Journal article (peer-reviewed)abstract
- The purpose of this project was to investigate the effects of Virtual Reality technology and haptics for stroke rehabilitation. Twenty-nine stroke subjects, 17 women, and 12 men aged 44-85 years, participated in three different studies. All participants responded favorable to the use of the VR activity station. A change of attitude took place after the subjects were exposed to playing computer games. The general experience with the VR application approach suggests that this treatment concept is promising in stroke rehabilitation, with a wide range of applicability.
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- Jendholm, Johan, et al.
(author)
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Moraxella catarrhalis-dependent tonsillar B cell activation does not lead to apoptosis but to vigorous proliferation resulting in nonspecific IgM production.
- 2008
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In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 83, s. 1370-1378
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Journal article (peer-reviewed)abstract
- The respiratory pathogen Moraxella catarrhalis has a high affinity for human IgD and is mitogenic for peripheral blood B lymphocytes. Moraxella IgD-binding protein, which is a multifunctional outer membrane protein with adhesive properties, is responsible for the interaction. Previous experiments with the Ig-binding B cell superantigens protein A and protein L from Staphylococcus aureus and Peptostreptococcus magnus, respectively, have suggested that nonimmune BCR cross-linking induces B cell apoptosis through the intrinsic pathway. The goal of this study was to characterize early and late B cell events in the presence of M. catarrhalis in comparison with S. aureus. Despite an increased phosphatidyl serine translocation as revealed by Annexin V binding in flow cytometry analyses, neither M. catarrhalis nor S. aureus induced activation-associated apoptotic cell death in purified human tonsillar B cells. In contrast, a vigorous B cell proliferation, as quantified using thymidine incorporation and CFSE staining, was observed. An increased expression of an array of surface proteins (i.e., CD19, CD21, CD40, CD45, CD54, CD69, CD86, CD95, and HLA-DR) and IgM production was found upon activation with M. catarrhalis. In conclusion, M. catarrhalis-dependent B cell activation does not result in apoptosis but in cell division and nonspecific IgM synthesis, suggesting that the bacterial interaction with tonsillar B cells serves to redirect the early adaptive immune response.
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9. |
- Lindqvist, Daniel, et al.
(author)
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Interleukin-6 Is Elevated in the Cerebrospinal Fluid of Suicide Attempters and Related to Symptom Severity
- 2009
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In: BIOLOGICAL PSYCHIATRY. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:3, s. 287-292
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Journal article (peer-reviewed)abstract
- Background: Depressive disorders are associated with immune system alterations that can be detected in the blood. Cytokine concentrations in cerebrospinal fluid (CSF) and their relationship to aspects of suicidality have previously not been investigated. Methods: We measured interleukin-1 beta interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-a (TNF-alpha) in CSF and plasma of suicide attempters (n = 63) and healthy control subjects (n = 47). Patients were classified according to diagnosis and violent or nonviolent suicide attempt. We evaluated suicidal ideation and depressive symptoms using the Suicide Assessment Scale and the Montgomery-Asberg Depression Rating Scale (MADRS). We also analyzed the relation between cytokines and monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in CSF, as well as the integrity of the blood-brain barrier as reflected by the CSF:serum albumin ratio. Results: IL-6 in CSF was significantly higher in suicide attempters than in healthy control subjects. Patients who performed violent suicide attempts displayed the highest IL-6. Furthermore, there was a significant positive correlation between MANS scores and CSF IL-6 levels in all patients. IL-6 and TNF-a correlated significantly with 5-HIAA and HVA in CSF, but not with MHPG. Cytokine levels in plasma and CSF were not associated, and patients with increased blood-brain barrier permeability did not exhibit elevated cytokine levels. Conclusions: We propose a role for CSF IL-6 in the symptomatology of suicidal behavior, possibly through mechanisms involving alterations of dopamine and serotonin metabolism.
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- Nordström, Therése, et al.
(author)
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The IgD-binding domain of the Moraxella IgD-binding protein MID (MID962-1200) activates human B cells in the presence of T cell cytokines.
- 2006
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In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 79:2, s. 319-329
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Journal article (peer-reviewed)abstract
- Moraxella catarrhalis immunoglobulin D (IgD)-binding protein (MID) is an outer membrane protein with specific affinity for soluble and cell-bound human IgD. Here, we demonstrate that mutated M. catarrhalis strains devoid of MID show a 75% decreased activation of human B cells as compared with wild-type bacteria. In contrast to MID-expressing Moraxella, the MID-deficient Moraxella mutants did not bind to human CD19(+) IgD(+) B cells. The smallest MID fragment with preserved IgD-binding capacity comprises 238 amino acids (MID962-1200). To prove the specificity of MID962-1200 for IgD, a Chinese hamster ovary (CHO) cell line expressing membrane-anchored human IgD was manufactured. MID962-1200 bound strongly to the recombinant IgD on CHO cells. Moreover, MID962-1200 stimulated peripheral blood lymphocyte (PBL) proliferation 5- and 15-fold at 0.1 and 1.0 mu g/ml, respectively. This activation could be blocked completely by antibodies directed against the CD40 ligand (CD154). MID962-1200 also activated purified B cells in the presence of interleukin (IL)-2 or IL-4. An increased IL-6 production was seen after stimulation with MID962-1200, as revealed by a human cytokine protein array. MID962-1200 fused to green fluorescent protein (GFP) bound to human B cells and activated PBL to the same degree as MID962-1200 Taken together, MID is the only IgD-binding protein in Moraxella. Furthermore, the novel T cell-independent antigen MID962-1200 may, together with MID962-1200-GFP, be considered as promising reagents in the study of IgD-dependent B cell activation.
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- Pellagatti, Andrea, et al.
(author)
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Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q-syndrome patients
- 2007
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:27, s. 11406-11411
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Journal article (peer-reviewed)abstract
- Myelodysplastic syndromes (MDSs) are a group of hematopoietic stem cell disorders characterized by ineffective hernatopoiesis and peripheral blood cytopenias. Lenalidomide has dramatic therapeutic effects in patients with low-risk MDS and a chromosome 5q31 deletion, resulting in complete cytogenetic remission in >60% of patients. The molecular basis of this remarkable drug response is unknown. To gain insight into the molecular targets of lenaliclomide we investigated its in vitro effects on growth, maturation, and global gene expression in isolated erythroblast cultures from MDS patients with clel(5)(q3l). Lenalidomide inhibited growth of differentiating del(5q) erythroblasts but did not affect cytogenetically normal cells. Moreover, lenalidomide significantly influenced the pattern of gene expression in del(5q) intermediate erythroblasts, with the V51G4, PPIC, TPBG, activin A, and SPARC genes up-regulated by >2-fold in all samples and many genes involved in erythropoiesis, including HBA2, GYPA, and KLF1, down-regulated in most samples. Activin A, one of the most significant differentially expressed genes between lenalidomide-treated cells from MDS patients and healthy controls, has pleiotropic functions, including apoptosis of hematopoietic cells. Up-regulation and increased protein expression of the tumor suppressor gene SPARC is of particular interest because it is anti proliferative, antiadhesive, and antiangiogenic and is located at 5q3l-q32, within the commonly deleted region in MDS 5q- syndrome. We conclude that lenalidomide inhibits growth of del(5q) erythroid progenitors and that the up-regulation of SPARC and activin A may underlie the potent effects of lenalidomide in MDS with clel(5)(q3l). SPARCmay play a role in the pathogenesis of the 5q- syndrome.
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15. |
- Ragnarsdottir, Bryndis, et al.
(author)
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Reduced Toll-like receptor 4 expression in children with asymptomatic bacteriuria
- 2007
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196:3, s. 475-484
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Journal article (peer-reviewed)abstract
- Toll-like receptor (TLR) 4 is essential for the defense against infection with gram-negative pathogens, but reduced TLR4 expression has not been linked to altered disease susceptibility in humans. In mice, Tlr4 controls the mucosal response to Escherichia coli urinary tract infections. Inactivation of mouse Tlr4 causes an asymptomatic carrier state resembling asymptomatic bacteriuria (ABU). The present study compared neutrophil TLR4 expression levels between children with ABU (n = 17) and age-matched control subjects (n = 24), and significantly lower levels were detected in the patients with ABU. We also found elevated levels of the TLR4 adaptor protein TRIF and reduced levels of the TLR4-inhibitor SIGIRR in the patients with ABU, but MyD88 and TRAM levels were not significantly altered. Altered TLR4 and adaptor protein expression might impair TLR4 signaling and explain the weak mucosal response to urinary tract infection in patients who develop ABU rather than symptomatic disease.
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16. |
- Rutter, Nick, et al.
(author)
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Evaluation of forest snow processes models (SnowMIP2)
- 2009
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In: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 114:6
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Journal article (peer-reviewed)abstract
- Thirty-three snowpack models of varying complexity and purpose were evaluated across a wide range of hydrometeorological and forest canopy conditions at five Northern Hemisphere locations, for up to two winter snow seasons. Modeled estimates of snow water equivalent (SWE) or depth were compared to observations at forest and open sites at each location. Precipitation phase and duration of above-freezing air temperatures are shown to be major influences on divergence and convergence of modeled estimates of the subcanopy snowpack. When models are considered collectively at all locations, comparisons with observations show that it is harder to model SWE at forested sites than open sites. There is no universal "best'' model for all sites or locations, but comparison of the consistency of individual model performances relative to one another at different sites shows that there is less consistency at forest sites than open sites, and even less consistency between forest and open sites in the same year. A good performance by a model at a forest site is therefore unlikely to mean a good model performance by the same model at an open site (and vice versa). Calibration of models at forest sites provides lower errors than uncalibrated models at three out of four locations. However, benefits of calibration do not translate to subsequent years, and benefits gained by models calibrated for forest snow processes are not translated to open conditions.
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17. |
- Samuelsson, Martin
(author)
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Characterization of IgD-binding by respiratory pathogens.
- 2006
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Doctoral thesis (other academic/artistic)abstract
- The focus of this thesis was to explore the interaction between IgD and Moraxella catarrhalis and Haemophilus influenzae. These two respiratory pathogens are responsible for otitis media in children, and exacerbations in patients afflicted with predisposing conditions such as chronic obstructive pulmonary disease (COPD). Both M. catarrhalis and H. influenzae have been shown to bind IgD in a non-immune manner. The binding of IgD by M. catarrhalis is mediated through Moraxella IgD-binding protein MID, whereas the IgD receptor on H. influenzae is not yet identified. The region of MID that interacts with IgD has previously been mapped to reside within amino acids 962-1200 (MID962-1200). A consequence of an IgD binding phenotype is the ability to activate B cells, and in this study we found that purified MID962-1200 had the capacity to activate B cells without the physical presence of T cells. In addition, we showed that for efficient B cell activation, the addition of the cytokines IL-4 or IL-2 was necessary. Furthermore, since MID has a unique specificity for IgD, we were able to use MID to selectively purify IgD from human serum. To in detail characterize the site on the IgD molecule responsible for the interaction with M. catarrhalis and H. influenzae, we manufactured a series of recombinant IgD molecules. Upon replacement of IgD with corresponding IgG sequences, we were able to determine that the IgD CH1 region contained the binding site for both species. In addition, we determined that IgD CH1 amino acids 198-224 were the interacting residues and that amino acids 198-206 were crucial for the interaction. In conclusion, the work presented in this thesis shows that the MID protein is capable of activating B cells without T cell help, and that it accomplishes this by binding to IgD CH1 amino acids 198-224. H. influenzae displays a similar IgD binding pattern as MID, and therefore the proteins may be similar. In addition, we developed a novel technique to selectively purify IgD from human serum by the use of recombinant MID.
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18. |
- Samuelsson, Martin, et al.
(author)
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Characterization of the IgD binding site of encapsulated Haemophilus influenzae serotype b.
- 2007
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In: Journal of Immunology. - 1550-6606. ; 178:10, s. 6316-6319
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Journal article (peer-reviewed)abstract
- Encapsulated Haemophilus influenzae is a causative agent of invasive disease, such as meningitis and septicemia. Several interactions exist between H. influenzae and the human host. H. influenzae has been reported to bind IgD in a nonimmune manner, but the responsible protein has not yet been identified. To define the binding site on IgD for H. influenzae, full-length IgD and four chimeric IgDs with interspersed TgG sequences and Ag specificity for dansyl chloride were expressed in stably transfected Chinese hamster ovary cells. The binding of recombinant IgD to a panel of encapsulated H. influenzae serotype b (Hib) and nontypeable strains were investigated using a whole cell ELISA and flow cytometry. IgD binding was detected in 50% of the encapsulated Hib strains examined, whereas nontypeable H. influenzae did not interact with IgD. Finally, mapping experiments using the chimeric IgD/IgG indicated that IgD C(H)1 aa 198-224 were involved in the interaction between IgD and H. influenzae. Thus, by using recombinant IgD and chimeras with defined Ag specificity, we have confirmed that Hib specifically binds IgD, and that this binding involves the IgD CHI region.
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- Samuelsson, Martin, et al.
(author)
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Purification of IgD from human serum - A novel application of recombinant M. catarrhalis IgD-binding protein (MID).
- 2006
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In: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 317, s. 31-37
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Journal article (peer-reviewed)abstract
- Moraxella catarrhalis IgD-binding protein (MID) is a multimeric outer membrane protein belonging to the family of autotransporters. The IgD-binding domain of MID is located between amino acids MID 962-1200 and binds to amino acids 198-224 of the IgD C(H)1 region. In the present study, we describe a method to purify IgD from serum with high levels of IgD using a two-step affinity chromatography process. The first step involves depletion of MID-specific antibodies of all classes from serum using the non-IgD-binding fragment MID1000-1200. This step is followed by selective capture of IgD with MID962-1200. Furthermore, we demonstrate that the eluted IgD is pure, intact and functional for use in downstream applications. Our approach reduces the non-specificity commonly associated with lectin-based IgD purification regimes that rely on glycosylation of the IgD molecule. (c) 2006 Elsevier B.V. All rights reserved.
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- Samuelsson, Martin, et al.
(author)
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Taurine in plasma and CSF : a study in healthy male volunteers
- 2009
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In: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 36:3, s. 529-33
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Journal article (peer-reviewed)abstract
- In order to explore the interrelationship between plasma and cerebrospinal fluid taurine concentrations, three consecutive 6-ml fractions of cerebrospinal fluid were drawn from 30 healthy male volunteers in the early morning after 8 h in the fasting condition. Repeated plasma samples were drawn over 24 h the day before lumbar puncture. Taurine in plasma and cerebrospinal fluid was determined by high performance liquid chromatography. The subjects were categorized as extensive or poor metabolizers with respect to the cytochrome P450 2D6 genotype. The taurine cerebrospinal fluid/plasma ratio at 8 a.m. was negatively influenced by the plasma taurine concentration at 4 p.m. the previous day. It was also negatively influenced by body mass index and positively by the intraspinal pressure. Three poor metabolizers of cytochrome P450 2D6 had higher plasma taurine areas under the curve than 27 extensive metabolizers. Hypothetically, cytochrome P450 2D6 influences the transport of taurine across the blood-brain barrier.
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23. |
- Samuelsson, Martin, et al.
(author)
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The IgD C(H)1 region contains the binding site for the human respiratory pathogen Moraxella catarrhalis IgD-binding protein MID.
- 2006
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In: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 9:Sep;36, s. 2525-2534
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Journal article (peer-reviewed)abstract
- The Moraxella catarrhalis IgD-binding protein (MID) has a unique specificity for human IgD, and the sequence with maximal IgD binding is located within the amino acids MID962-1200. In the present paper, we examined the MID binding site on IgD using a series of recombinant Ig. Full-length IgD, IgD F(ab')(2), and an IgD F(ab') C290R mutant lacking the inter-heavy-chain cysteine 290 were manufactured. Furthermore, a series of IgD/IgG chimeras were constructed. ELISA, dot blot and flow cytometry were used to study the binding of purified Ig to native MID, recombinant MID912-1200 or to Moraxella with or without MID. MID962-1200 bound both the IgD F(ab')(2) and F(ab') C290R, indicating that the binding occurred independently of antibody structure. When amino acids 157-224 of the IgD C(H)1 region were substituted with IgG sequences, binding by M. catarrhalis or recombinant MID962-1200 was abolished. Subsequent smaller substitutions of IgD C(H)1 157-224 with IgG sequences led us to conclude that IgD C(H)1 amino acids 198-206 were crucial for the interaction between MID and IgD.
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24. |
- Samuelsson, Yvonne, et al.
(author)
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Alignment Tools for Parallel Treebanks
- 2007
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In: Data Structures for Linguistic Resources and Applications. - 9783823363149
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Conference paper (peer-reviewed)abstract
- This paper reports about our efforts in creating a tri-lingual parallel treebank. The focal points are consistency checking and all aspects of sub-sentential alignment. We discuss the alignment guidelines, the importance of quality checks, and special alignment problems. Then we look at alignment algorithms and alignment visualization tools and we compare our own TreeAligner with other alignment tools. Our constituent structure treebanks contain just over 1,000 sentences and around 18,000 tokens in each language.
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25. |
- Samuelsson, Yvonne, et al.
(author)
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Automatic Phrase Alignment: Using Statistical N-Gram Alignment for Syntactic Phrase Alignment
- 2007
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In: Proceedings of the Sixth International Workshop on Treebanks and Linguistic Theories (TLT 2007). - : Northern European Association for Language Technology (NEALT). ; , s. 139-150
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Conference paper (peer-reviewed)abstract
- A parallel treebank consists of syntactically annotated sentences in two or more languages, taken from translated documents. These parallel sentences are linked through alignment. This paper explores the use of word n-gram alignment, computed for statistical machine translation, to create syntactic phrase alignment. We achieve a weighted F0.5-score of over 65%.
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26. |
- Sköld, Martin, et al.
(author)
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Regression analysis and modelling of data acquisition for SELDI-TOF mass spectrometry
- 2007
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 23:11, s. 1401-1409
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Journal article (peer-reviewed)abstract
- Motivation: Pre-processing of SELDI-TOF mass spectrometry data is currently performed on a largel y ad hoc basis. This makes comparison of results from independent analyses troublesome and does not provide a framework for distinguishing different sources of variation in data. Results: In this article, we consider the task of pooling a large number of single-shot spectra, a task commonly performed automatically by the instrument software. By viewing the underlying statistical problem as one of heteroscedastic linear regression, we provide a framework for introducing robust methods and for dealing with missing data resulting from a limited span of recordable intensity values provided by the instrument. Our framework provides an interpretation of currently used methods as a maximum-likelihood estimator and allows theoretical derivation of its variance. We observe that this variance depends crucially on the total number of ionic species, which can vary considerably between different pooled spectra. This variation in variance can potentially invalidate the results from naive methods of discrimination/classification and we outline appropriate data transformations. Introducing methods from robust statistics did not improve the standard errors of the pooled samples. Imputing missing values however—using the EM algorithm—had a notable effect on the result; for our data, the pooled height of peaks which were frequently truncated increased by up to 30%.
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