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| 4. |
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| 5. |
- Einarsdottir, E., et al.
(författare)
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CELSR2 is a candidate susceptibility gene in idiopathic scoliosis
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.
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| 6. |
- Chaudhary, Himanshu, et al.
(författare)
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Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases
- 2021
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:23, s. 26721-26734
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Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency in amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb10 and TiNb9, can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb10 or TiNb9 reduces the S100A9 amyloid formation rate and amyloid quantity. Atomic force microscopy imaging demonstrated the complete absence of long S100A9 amyloid fibrils at increasing concentrations of either POM and the presence of only round-shaped and slightly elongated aggregates. Molecular dynamics simulation revealed that both Nb10 and TiNb9 bind to native S100A9 homo-dimer by forming ionic interactions with the positively charged Lys residue-rich patches on the protein surface. The acrylamide quenching of intrinsic fluorescence showed that POM binding does not perturb the Trp 88 environment. The far and near UV circular dichroism revealed no large-scale perturbation of S100A9 secondary and tertiary structures upon POM binding. These indicate that POM binding involves only local conformational changes in the binding sites. By using intrinsic and 8-anilino-1-naphthalene sulfonate fluorescence titration experiments, we found that POMs bind to S100A9 with a Kd of ca. 2.5 μM. We suggest that the region, including Lys 50 to Lys 54 and characterized by high amyloid propensity, could be the key sequences involved in S1009 amyloid self-assembly. The inhibition and complete hindering of S100A9 amyloid pathways may be used in the therapeutic applications targeting the amyloid-neuroinflammatory cascade in neurodegenerative diseases.
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| 7. |
- Glesner, Jill, et al.
(författare)
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A Human IgE Antibody Binding Site on Der p 2 for the Design of a Recombinant Allergen for Immunotherapy
- 2019
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 203:9, s. 2545-2556
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Tidskriftsartikel (refereegranskat)abstract
- Der p 2 is one of the most important allergens from the house dust mite Dermatophagoides pteronyssinus Identification of human IgE Ab binding epitopes can be used for rational design of allergens with reduced IgE reactivity for therapy. Antigenic analysis of Der p 2 was performed by site-directed mutagenesis based on the x-ray crystal structure of the allergen in complex with a Fab from the murine IgG mAb 7A1 that binds an epitope overlapping with human IgE binding sites. Conformational changes upon Ab binding were confirmed by nuclear magnetic resonance using a 7A1-single-chain variable fragment. In addition, a human IgE Ab construct that interferes with mAb 7A1 binding was isolated from a combinatorial phage-display library constructed from a mite-allergic patient and expressed as two recombinant forms (single-chain Fab in Pichia pastoris and Fab in Escherichia coli). These two IgE Ab constructs and the mAb 7A1 failed to recognize two Der p 2 epitope double mutants designed to abolish the allergen-Ab interaction while preserving the fold necessary to bind Abs at other sites of the allergen surface. A 10-100-fold reduction in binding of IgE from allergic subjects to the mutants additionally showed that the residues mutated were involved in IgE Ab binding. In summary, mutagenesis of a Der p 2 epitope defined by x-ray crystallography revealed an IgE Ab binding site that will be considered for the design of hypoallergens for immunotherapy.
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| 9. |
- Ohlin, M., et al.
(författare)
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Human antibody reactivity against the lower matrix protein (pp65) produced by cytomegalovirus
- 1995
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Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 2:3, s. 325-329
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Tidskriftsartikel (refereegranskat)abstract
- The lower matrix protein (pp65) is a major product of many laboratory strains of cytomegalovirus (CMV). It is thus an integral part of many CMV serological assays based on native antigen. Recombinant fragments of pp65 have previously been investigated for their usefulness in more-defined assays. The latter antigens have, however, failed to develop a positive response with serum samples derived from a substantial number of infected individuals. Here we show that the human humoral immune response to CMV pp65 is highly diverse and recognizes at least seven distinct but in some cases partly overlapping epitopes. Most of these epitopes could not be mimicked by any of the investigated recombinant or synthetic antigens. Furthermore, when we investigated the ability of human CMV-seropositive serum samples to block the reactivity of pp65 specific antibodies recognizing five different epitopes within pp65, it was evident that several sera did not contain significant levels of antibodies against any of these or overlapping structures. It was thus concluded that the antibody response against CMV pp65 is weak in some CMV-infected individuals, making this antigen unsuitable for use alone in serological screening systems for CMV infection.
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| 10. |
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| 11. |
- Dueñas, M., et al.
(författare)
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In vitro immunization of naive human B cells yields high affinity immunuglobulin G antibodies as illustrated by phage display
- 1996
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Ingår i: Immunology. - 0019-2805. ; 89:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- In vitro antibody responses to a synthetic immunogen, consisting of both a B cell [V3 loop of gp120 from human immunodeficiency virus type 1 (HIV-1)] and a T-helper epitope (15 amino acids of tetanus toxoid) was studied. The in vitro activation was performed by primary and secondary in vitro immunizations, using lymphocytes obtained from uninfected, seronegative donors. Analysis of the in vitro immune response demonstrated an antigen-specific isotype switch, which was dependent on the presence of antigen-specific T-helper cells, CD40 ligation and antigen. Antibody libraries were constructed from cells derived directly from the naive donors, or from primary or secondary in vitro immunized B cells. Five libraries were displayed on filamentous phage and selected for anti-V3-specific Fab fragments, using a selection approach that linked recognition and phage replication. A panel of 19 recombinant antigen-specific Fab, representing different phases of the humoral in vitro immune response, were sequenced, expressed and analysed using a biosensor. Recombinant Fab fragments derived from cultures on day 12 exhibited an increase in affinity of close to two orders of magnitude compared to those obtained from cells primary immunized for 7 days. This study provides the first evidence that an antigen-specific in vitro immune response can yield high-affinity immunoglobuling G antibodies.
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| 12. |
- Gharizadeh, B., et al.
(författare)
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Multiple group-specific sequencing primers for reliable and rapid DNA sequencing
- 2003
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Ingår i: Molecular and Cellular Probes. - : Elsevier BV. - 0890-8508 .- 1096-1194. ; 17:4, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- Pyrosequencing(TM) technology is a bioluminometric DNA sequencing method that employs a cascade of four enzymes to deliver sequence signals. To date this technology has been limited to the sequencing of short stretches of DNA. As an improvement to this technique, we have introduced a bacterial group-specific, multiple sequencing primer approach that circumvents sequencing of less informative semi-conservative regions of the 16S rRNA gene. This new approach is suitable for challenging templates, improving sequence data quality, avoiding sequencing of non-specific amplification products, lessening sequencing time, and moreover, this strategy should open the way for many new applications in the future. The group-specific, multiple sequencing primers can be applied in the Sanger dideoxy sequencing method as well. In addition, we have improved the chemistry of the Pyrosequencing system enabling sequencing of longer stretches of DNA, which allows numerous new applications.
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| 13. |
- Ljungars, A., et al.
(författare)
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A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
- 2018
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Ingår i: JCO Precision Oncology. - : Springer Science and Business Media LLC. - 2473-4284 .- 2397-768X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Development of antibody drugs against novel targets and pathways offers great opportunities to improve current cancer treatment. We here describe a phenotypic discovery platform enabling efficient identification of therapeutic antibody-target combinations. The platform utilizes primary patient cells throughout the discovery process and includes methods for differential phage display cell panning, high-throughput cell-based specificity screening, phenotypic in vitro screening, target deconvolution, and confirmatory in vivo screening. In this study the platform was applied on cancer cells from patients with Chronic Lymphocytic Leukemia resulting in discovery of antibodies with improved cytotoxicity in vitro compared to the standard of care, the CD20-specific monoclonal antibody rituximab. Isolated antibodies were found to target six different receptors on Chronic Lymphocytic Leukemia cells; CD21, CD23, CD32, CD72, CD200, and HLA-DR of which CD32, CD200, and HLA-DR appeared as the most potent targets for antibody-based cytotoxicity treatment. Enhanced antibody efficacy was confirmed in vivo using a patient-derived xenograft model.
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| 14. |
- Ohlin, M., et al.
(författare)
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Human MoAbs produced from normal, HIV-1-negative donors and specific for glycoprotein gp120 of the HIV-1 envelope
- 1992
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 89:2, s. 290-295
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Tidskriftsartikel (refereegranskat)abstract
- Human MoAbs ofIgM class were developed against three regions of the HIV-1 envelope. Uninfected donor lymphocytes were immunized in vitro with recombinant protein pB1. Four out of five antibodies were directed to different parts of the V3 region, which contains a major neutralizing site. Two out of these antibodies were directed to more than one amino acid sequence, indicating reactivity to discontinuous sites. Two of the human MoAbs inhibited viral spread between cells in tissue culture, interpreted as reactivities to conserved amino acid sequences exposed during viral maturation. No MoAb neutralized virus, which may be explained by the relatively low avidity of the antibodies. One MoAb was directed to a region containing amino acids participating in CD4 binding. This technique appears to allow formation of antibodies with fine specificities other than those obtained in infected hosts.
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| 15. |
- Ohlin, Mats, et al.
(författare)
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Inferred Allelic Variants of Immunoglobulin Receptor Genes : A System for Their Evaluation, Documentation, and Naming
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.
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| 16. |
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| 17. |
- Pautler, Brent G., et al.
(författare)
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A High-Pressure NMR Probe for Aqueous Geochemistry
- 2014
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 53:37, s. 9788-9791
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Tidskriftsartikel (refereegranskat)abstract
- A non-magnetic piston-cylinder pressure cell is presented for solution-state NMR spectroscopy at geochemical pressures. The probe has been calibrated up to 20kbar using insitu ruby fluorescence and allows for the measurement of pressure dependencies of a wide variety of NMR-active nuclei with as little as 10L of sample in a microcoil. Initial (BNMR)-B-11 spectroscopy of the H3BO3-catechol equilibria reveals a large pressure-driven exchange rate and a negative pressure-dependent activation volume, reflecting increased solvation and electrostriction upon boron-catecholate formation. The inexpensive probe design doubles the current pressure range available for solution NMR spectroscopy and is particularly important to advance the field of aqueous geochemistry.
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| 18. |
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| 19. |
- Säll, Anna, et al.
(författare)
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Generation and analyses of human synthetic antibody libraries and their application for protein microarrays
- 2016
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press. - 1741-0126 .- 1741-0134. ; 29:10, s. 427-437
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization.
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| 20. |
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| 21. |
- Andersson, Eva, et al.
(författare)
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CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells
- 1995
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 163:2, s. 245-253
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Tidskriftsartikel (refereegranskat)abstract
- A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.
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| 22. |
- Andersson, Eva, et al.
(författare)
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Immunoglobulin production induced by CD57+ GC-derived helper T cells in vitro requires addition of exogenous IL-2
- 1996
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 169:2, s. 166-173
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Tidskriftsartikel (refereegranskat)abstract
- Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+ T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+CD57+ GC T cells to become activated and to take part in B cell activation processes, These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25, The cell population was found neither to containe nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-γ upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+ T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures, However, despite their apparent lack of function CD4+CD57+ GC T cells were found to rescue GC B cells from cell death in vitro to the same extent as CD4+CD57- T(h) cells, The phenotypical and functional differences found between these T cells and regular T(h)-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, Irate in the immune response, having lost most of their original functions and capabilities.
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| 23. |
- Andersson, J., et al.
(författare)
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Neonatal pneumothorax : symptoms, signs and timing of onset in the post-surfactant era
- 2022
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Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa Healthcare. - 1476-7058 .- 1476-4954. ; 35:25, s. 5438-5442
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The primary objective was to describe the incidence, symptoms, clinical signs, and time of onset of neonatal pneumothorax in Örebro County during 2011-2017. Secondary objectives were to describe risk factors, diagnostic procedures, treatments, and mortality and to compare preterm with term/post-term neonates.MATERIALS AND METHODS: This retrospective population-based descriptive study included all neonates born in Örebro County during 2011-2017 and admitted to the neonatal intensive care unit at Örebro University Hospital at age <28 days with an x-ray verified diagnosis of "Pneumothorax originating in the perinatal period" in their medical record.RESULTS: Seventy-five neonates matched the inclusion criteria. The incidence of neonatal pneumothorax in Örebro County during the study period was 3.1 (95% CI: 2.5-3.8) per 1000 live births. All neonates were <48 h at debut of respiratory symptoms and the most common symptom was tachypnea. Twelve (16%) received invasive treatment. The mortality rate was 2 (3%), none due to pneumothorax.CONCLUSION: The incidence of 3.1 per 1000 live births was relatively high, but the frequency of invasive treatment and mortality was low, indicating a high proportion of mild pneumothoraces. The lack of patients aged >48 h indicates that most neonatal pneumothoraces now occur very early in life.
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| 24. |
- Aureliano, Manuel, et al.
(författare)
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Characterization of decavanadate and decaniobate solutions by Raman spectroscopy
- 2016
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 45:17, s. 7391-7399
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Tidskriftsartikel (refereegranskat)abstract
- The decaniobate ion, (Nb-10 = [Nb10O28](6-)) being isoelectronic and isostructural with the decavanadate ion (V-10 = [V10O28](6-)), but chemically and electrochemically more inert, has been useful in advancing the understanding of V-10 toxicology and pharmacological activities. In the present study, the solution chemistry of Nb-10 and V-10 between pH 4 and 12 is studied by Raman spectroscopy. The Raman spectra of V-10 show that this vanadate species dominates up to pH 6.45 whereas it remains detectable until pH 8.59, which is an important range for biochemistry. Similarly, Nb-10 is present between pH 5.49 and 9.90 and this species remains detectable in solution up to pH 10.80. V-10 dissociates at most pH values into smaller tetrahedral vanadate oligomers such as V-1 and V-2, whereas Nb-10 dissociates into Nb-6 under mildly (10 > pH > 7.6) or highly alkaline conditions. Solutions of V-10 and Nb-10 are both kinetically stable under basic pH conditions for at least two weeks and at moderate temperature. The Raman method provides a means of establishing speciation in the difficult niobate system and these findings have important consequences for toxicology activities and pharmacological applications of vanadate and niobate polyoxometalates.
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| 25. |
- Babrak, Lmar, et al.
(författare)
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Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IG Gene Annotation
- 2022
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Ingår i: Immunogenetics : Methods and Protocols - Methods and Protocols. - New York, NY : Springer US. - 1064-3745. - 9781071621158 - 9781071621141 ; 2453, s. 279-296
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Bokkapitel (refereegranskat)abstract
- High-throughput sequencing of adaptive immune receptor repertoires (AIRR, i.e., IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-specific or immune-state-associated signatures of immune responses, study the development of the antibody immune response, and guide the development of vaccines and antibody therapies. Recent advancements in the technology include sequencing at the single-cell level and in parallel with gene expression, which allows the introduction of multi-omics approaches to understand in detail the adaptive immune response. Analyzing AIRR-seq data can prove challenging even with high-quality sequencing, in part due to the many steps involved and the need to parameterize each step. In this chapter, we outline key factors to consider when preprocessing raw AIRR-Seq data and annotating the genetic origins of the rearranged receptors. We also highlight a number of common difficulties with common AIRR-seq data processing and provide strategies to address them.
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| 26. |
- Borrebaeck, Carl A K, et al.
(författare)
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Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as cancer therapeutics?
- 1993
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Ingår i: Immunology Today. - 0167-5699. ; 14:10, s. 477-479
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies have many potential therapeutic benefits. However, when applied to humans, mouse monoclonal antibodies have several disadvantages. Here Carl Borrebaeck and colleagues describe a strategy to overcome the anti-Gal activity, thought to be one of the reasons why mouse mAbs have a limited half-life.
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| 27. |
- Borrebaeck, Carl A K, et al.
(författare)
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Kinetic analysis of recombinant antibody-antigen interactions : Relation between structural domains and antigen binding
- 1992
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Ingår i: Bio/Technology. - : Springer Science and Business Media LLC. - 0733-222X. ; 10:6, s. 697-698
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Tidskriftsartikel (refereegranskat)abstract
- The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 X 109 M-1 and 25 X 109 M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.
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| 28. |
- Brorson, Håkan, et al.
(författare)
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Suction-assisted lipectomy
- 2015
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Ingår i: Lymphedema : Presentation, Diagnosis, and Treatment - Presentation, Diagnosis, and Treatment. - Cham : Springer International Publishing. - 9783319144924 - 9783319144931 ; , s. 313-324
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Bokkapitel (refereegranskat)abstract
- 39.Brorson H, Svensson B, Ohlin K. Suction-Assisted Lipectomy. In: Greene AK, Slavin S, Brorson H, editors, Lymphedema - Presentation, Diagnosis, and Treatment. Cham, Switzerland: Springer; 2015: p. 313-324.
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| 29. |
- Brorson, Håkan, et al.
(författare)
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Volume measurements and follow-up
- 2015
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Ingår i: Lymphedema : Presentation, Diagnosis, and Treatment - Presentation, Diagnosis, and Treatment. - Cham : Springer International Publishing. - 9783319144924 - 9783319144931 ; , s. 115-122
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Bokkapitel (refereegranskat)
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| 30. |
- Carlsson, Fredrika, et al.
(författare)
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Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines.
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein B (gB) is a major component in several vaccines that are under development for prevention of disease by cytomegalovirus. It contains multiple determinants that are targets for neutralizing antibodies. One of them is site I of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite conserved between different isolates. However, it is poorly immunogenic in natural infection. In this study we investigated the extent to which different vaccines, attenuated live Towne vaccine with or without priming with a canarypox virus coding for gB, or a recombinant gB vaccine adjuvanted with MF59, induced antibodies to this epitope. As in natural infection only a fraction of all subjects developed antibody responses against site I of AD-2 following vaccination. We suggest that strategies that enhance immunogenicity of this epitope will improve vaccine efficacy.
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| 31. |
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| 32. |
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| 33. |
- Chin, L. T., et al.
(författare)
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Site-directed primary in vitro immunization : Production of HIV-1 neutralizing human monoclonal antibodies from lymphocytes obtained from seronegative donors
- 1994
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Ingår i: Immunology. - 0019-2805. ; 81:3, s. 428-434
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Tidskriftsartikel (refereegranskat)abstract
- The design of an in vitro immunization system based on a synthetic heterotope immunogen, which was a peptide containing both T- and B-cell epitopes, that elicited a neutralizing, primary human humoral immune response against the human immunodeficiency virus (HIV-1) is reported here. This heterotope construct contained the major neutralizing B-cell epitope, within the V3 region of glycoprotein 120 (gp120), linked to a promiscuous helper T- cell epitope of tetanus toxin. The peptide was used to induce a human humoral in vitro immune response against the V3 region, using lymphocytes obtained from healthy, sero-negative blood donors. The in vitro immunized peripheral blood lymphocytes were Epstein-Barr virus infected and the antibody response to the synthetic peptide was evaluated using a solid-phase ELISA with the recombinant C-terminal fragment of gp120 (pB1, amino acid residues 287 467, derived from the HIV-1 LAI isolate). The heterotope construct yielded a significant frequency of specifically immunized B cells, in contrast to the control immunizations with individual T and B epitopes mixtures of these epitopes or no immunogen at all. This approach allowed us to generate human monoclonal antibodies, using lymphocytes derived from sero-negative donors, that cross-neutralized several HIV-1 strains, inhibited syncytia formation as well as prevented spreading of the viral infection from cell to cell. Thus, site-directed in vitro immunization using synthetic heterotopes might prove valuable in the dissection and induction of a protective humoral immune response.
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| 34. |
- Colla, Christopher A., et al.
(författare)
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Computational prediction of Mg-isotope fractionation between aqueous [Mg(OH2)6]2+ and brucite
- 2018
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533. ; 227, s. 64-74
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Tidskriftsartikel (refereegranskat)abstract
- The fractionation factor in the magnesium-isotope fractionation between aqueous solutions of magnesium and brucite changes sign with increasing temperature, as uncovered by recent experiments. To understand this behavior, the Reduced Partition Function Ratios and isotopic fractionation factors (Δ26/24Mgbrucite-Mg(aq)) are calculated using molecular models of aqueous [Mg(OH2)6]2+ and the mineral brucite at increasing levels of density functional theory. The calculations were carried out on the [Mg(OH2)6]2+·12H2O cluster, along with different Pauling-bond-strength-conserving models of the mineral lattice of brucite. Three conclusions were reached: (i) all levels of theory overestimate 〈Mg‒O〉 bond distances in the aqua ion complex relative to Tutton’s salts; (ii) the calculations predict that brucite at 298.15 K is always enriched in the heavy isotope, in contrast with experimental observations; (iii) the temperature dependencies of Wimpenny et al. (2014) and Li et al. (2014) could only be achieved by fixing the 〈Mg‒O〉 bond distances in the [Mg(OH2)6]2+·12H2O cluster to values close to those observed in crystals that trap the hydrated ion.
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| 35. |
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| 36. |
- Cruz, Silian, et al.
(författare)
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Mouse monoclonal antibodies against outer membrane proteins of a vaccine strain of Neisseria meningitidis B : 4:P1.15
- 1998
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Ingår i: Minerva Biotecnologica. - 1120-4826. ; 10:2, s. 65-70
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Tidskriftsartikel (refereegranskat)abstract
- Background. Neisseria meningitidis (Nm) is a Gram negative diplococcus causing bacterial meningitis and fulminant septicemia. In order to allow efficient characterization of infecting strains, antibody reagents for use as analytical tools have proven to be invaluable tools. Similarly, antibodies against relevant bacterial antigens may guide in the selection of components to be included in developing vaccine strategies. Methods. We have thus developed mouse monoclonal antibodies specific for class 1, 3 and 5 antigens expressed by the B:4:P1.15 isolate CU385/83, also being used in a recently developed protective vaccine. In particular, two antibodies CB-Nm.1 and CB- Nm.2 recognize epitopes partly overlapping the subserotype (class 1 antigens) and serotype (class 3 antigen) specificities detected by the previously defined antibodies C6 and 15-1-P4 respectively, were evaluated. Results. As judged by strain recognition, the absolute requirement for binding differs between both the class 1-specific and class 3 specific antibodies suggesting the importance of using multiple antibodies when evaluating subserotype/serotype characteristics of clinical isolates of Nm by serological methods. Conclusion. Furthermore, the development of antibodies crossreactive with subserotype/serotype antigens may partly explain the ability of outer membrane protein vaccine to induce protective activity against strains considered as carrying different class 1 and 3 antigens as determined by available (sub)serotyping reagents.
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| 37. |
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| 38. |
- De Cossío, Maria E Fernández, et al.
(författare)
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Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis
- 1992
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 166:6, s. 1322-1328
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Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis is a causative agent of meningitis. Despite vaccination programs, it still causes a large number of deaths in young children. Early diagnosis followed by passive immunization with human monoclonal antibodies could be an approach to effective therapy. Peripheral blood lymphocytes from normal, healthy blood donors and from vaccinated individuals were immunized in vitro, using outer membrane proteins purified from A. meningitidis B:4:P1,15. The immunized human B cells were Epstein-Barr virus transformed and fused to a heteromyeloma. Several stable human hybridoma cell lines were established and two, secreting antibodies against the 31-kDa class 5c outer membrane protein, were characterized further. The human antibodies were of IgG1 and IgG3 isotypes, with κ light chains. The recognized epitope was commonly found among pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies may be important in the evaluation of N. meningitidis infections.
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| 39. |
- Dueñas, M., et al.
(författare)
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A point mutation in a murine immunoglobulin V-region strongly influences the antibody yield in Escherichia coli
- 1995
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Ingår i: Gene. - 0378-1119. ; 158:1, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant DNA technology has made it possible to produce specific Fab and scFv antibody (Ab) fragments in prokaryotic host cells. Using vectors designed for periplasmic expression of encoded Ab fragments, we have been studying how the sequence and genetic localization of the light chain (L-chain) variable region gene of a mouse Ab (CB-Nm.1) determined the level of Ab production. The variable region was shown to belong to the VKV family and contained a previously unreported Ile72. Nine different Ab constructions were tested in monocistronic (scFv) or dicistronic (Fab) operons for their ability to affect the synthesis level of the L-chain. When the gene coding for the L-chain was located downstream from the Fd fragment gene, the substitution of codons encoding Ile by a codon encoding Thr was found to be crucial for any expression of the L-chain fragment. This was, however, not accompanied by an increase in L-chain-specific mRNA, neither was there any change in the size of the mRNA. The fact that the unmutated L-chain protein was produced from cells transformed with certain other constructions indicated that the protein as such was not incompatible with the prokaryotic environment. Together, this suggested that the translation process was involved in the restricted production of the L-chain. Thus, surprisingly small substitutions significantly affected the expression level, a fact that will have important implications on the library size expressed in prokaryotic hosts, including phagedisplayed Ab libraries.
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| 40. |
- Duenas, M., et al.
(författare)
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Intra- and extracellular expression of an scFv antibody fragment in E. coli : Effect of bacterial strains and pathway engineering using GroES/L chaperonins
- 1994
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Ingår i: BioTechniques. - 0736-6205. ; 16:3, s. 476-480
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of bacterial host on the secretion of single-chain Fv antibody fragment (scFv), the production of this antibody fragment as intracellular fusion protein, and the effect of chaperonin coexpression on intracellular antibody expression. Seven bacterial strains were transformed with a vector carrying the genes encoding the variable regions of an anti-CEA scFv antibody and the ompA leader sequence (ptrp/ompA/scFvCEA). Expression and secretion of this antibody fragment were highest in the W3110 strain, as determined by Western blot analysis and enzyme immunoassay, where the scFv fragment amounted to approximately 30% of the total periplasmic protein. Except for BMH71-18, the other strains were unsuitable for antibody fragment expression, suggesting screening of bacterial strains as an important parameter. For intracellular expression, the scFv was expressed as a fusion protein with a 26-amino acid N-terminal fragment of human interleukin-2 (IL-2), using the pIL-2f/scFvCEA vector. The fusion protein was expressed at 30% of total biomass and retained antigen binding after in vitro refolding. Co-expression of chaperonin encoding plasmic pGroES/L with pIL-2f/scFv increased the intracellular production of the fusion protein two-fold, with a similar increase in the final amount of active scFv antibody fragment that could be obtained after in vitro refolding. The chaperonins had no effect on secretion of scFv antibody fragments, using the ptrp/ompA/scFvCEA.
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| 41. |
- Dueñas, Marta, et al.
(författare)
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Selection of phage displayed antibodies based on kinetic constants
- 1996
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890. ; 33:3, s. 279-285
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Tidskriftsartikel (refereegranskat)abstract
- The display of antibody fragments on the surface of filamentous bacteriophages and the selection of binders from antibody libraries have provided powerful tools to generate human antibodies. We reported recently a new concept (SAP system) for the selection of specific phages by linking antigenic recognition and phage replication, using a soluble fusion protein containing the antigen and a fragment of the M13 coat protein 3. In this investigation, a model library has been composed using six different antibody fragments which were characterized individually regarding their k(ass), k(diss) and K(a). All Feb fragments were specific for a 15 amino acid region of the V3 loop of gp120 (HIV-1). We demonstrated that the SAP system could discriminate between the kinetic parameters of each clone, using different selection strategies. Phages expressing high affinity clones were selected preferentially using low doses of antigen but clones of lower affinity also could be selected by increasing the antigen concentration or using a preselection procedure. Phages expressing antibody fragment with high association or low dissociation rate constants were retrieved by utilizing short contact times between antigen and antibody or antigen-chase conditions.
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| 42. |
- Dyson, P J, et al.
(författare)
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Determination of hydrogen concentration in ionic liquids and the effect (or lack of) on rates of hydrogenation
- 2003
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; :19, s. 2418-2419
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Tidskriftsartikel (refereegranskat)abstract
- The solubility of hydrogen and the corresponding Henry coefficients for 11 ionic liquids have been determined in situ at 100 atm H(2) pressure and are much lower than expected; attempts to correlate the solubility of hydrogen in the ionic liquids with the rate of reaction for the hydrogenation of benzene to cyclohexane in these solvents have been made.
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| 43. |
- Faber, Catherine, et al.
(författare)
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Three-dimensional structure of a human Fab with high affinity for tetanus toxoid
- 1998
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Ingår i: Immunotechnology. - 1380-2933. ; 3:4, s. 253-270
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Tidskriftsartikel (refereegranskat)abstract
- Background: The wide range of antibody specificity and affinity results from the differing shapes and chemical compositions of their binding sites. These shapes range from discrete grooves in antibodies elicited by linear oligomers of nucleotides and carbohydrates to shallow depressions or flat surfaces for accommodation of proteins: peptides and large organic compounds. Objectives: To determine the Fab structure of a high-affinity human antitoxin antibody. To explore structural features which enable the antibody to bind to intact tetanus toxoid, peptides derived from the sequence of the natural immunogen and antigenic mimics identified by combinatorial chemistry. To explain why this Fab shows a remarkable tendency to produce crystals consistently diffracting to d spacings of 1.7-1.8 Å. To use this information to engineer a strong tendency to crystallize into the design of other Fabs. Study design: The protein was crystallized in hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG) 8000. Crystals were subjected to X-ray analysis and the three-dimensional structure of the Fab was determined by the molecular replacement method. Interactive computer graphics were employed to fit models to electron density maps, survey the structure in multiple views and discover the crystal packing motif of the protein. Results: Exceptionally large single crystals of this protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter was cut into six irregular pieces, each retaining the features of the original in diffracting to high resolution (1.8 Å) with little decay in the X-ray beam. In an individual Fab, the active site is relatively flat and it seems likely that the protein antigen and derivative peptides are tightly held on the outer surface without significant penetration into the interior. There is no free space to accommodate even a dipeptide between V(H) and V(L). One of the unique features of the B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site. The CDR3 of the H chain contributes significantly to this ridge, as well as to adjoining regions projected to be important for the docking of the antigen. Both the ease of crystallization and the favorable diffraction properties are mainly attributable to the tight packing of the protein molecules in the crystal lattice. Discussion: The B7-15A2 active site provides a stable and well defined platform for high affinity docking of proteins, peptides and their mimotopes. The advantages for future developments are suggested by the analysis of the crystal properties. It should be possible to incorporate the features promoting crystallization, close packing and resistance to radiation damage into engineered human antibodies without altering the desired specificities and affinities of their active sites.
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| 44. |
- Fraqueza, Gil, et al.
(författare)
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Decavanadate, decaniobate, tungstate and molybdate interactions with sarcoplasmic reticulum Ca2+-ATPase : quercetin prevents cysteine oxidation by vanadate but does not reverse ATPase inhibition
- 2012
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 41:41, s. 12749-12758
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Tidskriftsartikel (refereegranskat)abstract
- Recently we demonstrated that the decavanadate (V-10) ion is a stronger Ca2+-ATPase inhibitor than other oxometalates, such as the isoelectronic and isostructural decaniobate ion, and the tungstate and molybdate monomer ions, and that it binds to this protein with a 1 : 1 stoichiometry. The V-10 interaction is not affected by any of the protein conformations that occur during the process of calcium translocation (i.e. E1, E1P, E2 and E2P) (Fraqueza et al., J. Inorg. Biochem., 2012). In the present study, we further explore this subject, and we can now show that the decaniobate ion, [Nb-10 = Nb10O28](6-), is a useful tool in deducing the interaction and the non-competitive Ca2+-ATPase inhibition by the decavanadate ion [V-10 = V10O28](6-). Moreover, decavanadate and vanadate induce protein cysteine oxidation whereas no effects were detected for the decaniobate, tungstate or molybdate ions. The presence of the antioxidant quercetin prevents cysteine oxidation, but not ATPase inhibition, by vanadate or decavanadate. Definitive V(IV) EPR spectra were observed for decavanadate in the presence of sarcoplasmic reticulum Ca2+-ATPase, indicating a vanadate reduction at some stage of the protein interaction. Raman spectroscopy clearly shows that the protein conformation changes that are induced by V-10, Nb-10 and vanadate are different from the ones induced by molybdate and tungstate monomer ions. Here, Mo and W cause changes similar to those by phosphate, yielding changes similar to the E1P protein conformation. The putative reduction of vanadium(V) to vanadium(IV) and the non-competitive binding of the V-10 and Nb-10 decametalates may explain the differences in the Raman spectra compared to those seen in the presence of molybdate or tungstate. Putting it all together, we suggest that the ability of V-10 to inhibit the Ca2+-ATPase may be at least in part due to the process of vanadate reduction and associated protein cysteine oxidation. These results contribute to the understanding and application of these families of mono-and polyoxometalates as effective modulators of many biological processes, particularly those associated with calcium homeostasis.
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| 45. |
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| 46. |
- Fritzell, Peter, et al.
(författare)
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Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
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Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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| 47. |
- Furebring, Christina, et al.
(författare)
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Evaluation of novel control elements by construction of eukaryotic expression vectors
- 1997
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Ingår i: Gene. - 0378-1119. ; 188:2, s. 191-198
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Tidskriftsartikel (refereegranskat)abstract
- A novel mammalian eukaryotic expression vector for the production of immunoglobulin heavy chain (IgH) genes has been designed. This expression vector contains the variable heavy chain (VH) promoter, the IgH intron enhancer (μE) and the IgH 3' enhancer (3'E). This construct, designated pTIF-1, was stably transfected into the myeloma cell line J558L. A fivefold increase in the expression level of a rearranged IgH gene was observed when using the pTIF-1 vector containing the 3'E compared to an expression vector lacking this enhancer. Interestingly, this positive effect on the expression level of the 3' enhancer appears to be position independent. The introduction of two recently identified Ig control elements, HS3 and HS4, to the vector cassette did not further elevate the expression level in the cell line tested. The pTIF-1 vector can be used for expression of any antibody specificity, using PCR amplification of the VDJ region of interest. Furthermore, the constant region can easily be exchanged, which further facilitates studies to dissect different effector functions of IgH constant genes.
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| 48. |
- Furer, Sebastian O., et al.
(författare)
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The Performance-Determining Role of Lewis Bases in Dye-Sensitized Solar Cells Employing Copper-Bisphenanthroline Redox Mediators
- 2020
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Ingår i: Advanced Energy Materials. - : Wiley-VCH Verlagsgesellschaft. - 1614-6832 .- 1614-6840. ; 10:37
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Tidskriftsartikel (refereegranskat)abstract
- Copper redox mediators have enabled open-circuit voltages (V-OC) of over 1.0 V in dye-sensitized solar cells (DSCs) and have helped to establish DSCs as the most promising solar cell technology in low-light conditions. The addition of additives such as 4-tert-butylpyridine (tBP) to these electrolytes has helped in achieving high solar cell performances. However, emerging evidence suggests that tBP coordinates to the Cu(II) species and limits the performance of these electrolytes. To date, the implications of this coordination are poorly understood. Here, the importance of Lewis base additives for the successful implementation of copper complexes as redox mediators in DSCs is demonstrated. Two redox couples, [Cu(dmp)(2)](+/2+)and [Cu(dpp)(2)](+/2+)(with dmp = 2,9-dimethyl-1,10-phenanthroline and dpp = 2,9-diphenyl-1,10-phenanthroline) in combination with three different Lewis bases, TFMP (4-(trifluoromethyl)pyridine), tBP, and NMBI (1-methyl-benzimidazole), are considered. Through single-crystal X-ray diffraction analysis, absorption, and(1)H-NMR spectroscopies, the coordination of Lewis bases to the Cu(II) centers are studied. This coordination efficiently suppresses recombination losses and is crucial for high performing solar cells. If, however, the coordination involves a ligand exchange, as is the case for [Cu(dpp)(2)](+/2+), the redox mediator regeneration at the counter electrode is significantly retarded and the solar cells show current limitations.
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| 49. |
- Gerdhem, P., et al.
(författare)
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Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls
- 2015
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 24:2, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis. We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons. COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (beta = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (beta = 0.27, p = 0.007), but not in children without scoliosis (beta = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (beta = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (beta = -0.16; p = 0.14). COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.
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| 50. |
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