| 1. |
- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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| 2. |
- Jamil, S., et al.
(författare)
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Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme
- 2013
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 43:3, s. 831-838
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stem-cell induced mature teratoma can function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cell-induced teratoma (PSCT) and compared to xenografts of the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a non-random fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma, resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics, or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.
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| 3. |
- Jamil, Seema, et al.
(författare)
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Tropism of the in situ growth from biopsies of childhood neuroectodermal tumors following transplantation into experimental teratoma
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:7, s. 1630-1637
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Tidskriftsartikel (refereegranskat)abstract
- Experimental teratoma induced from human pluripotent stem cells with normal karyotype can be described as a failed embryonic process and includes besides advanced organoid development also large elements of tissue with a prolonged occurrence of immature neural components. Such immature components, although benign, exhibit strong morphological resemblance with tumors of embryonic neuroectodermal origin. Here, we demonstrate that biopsy material from childhood tumors of neural embryonic origin transplanted to mature experimental teratoma can show an exclusive preference for matching tissue. Tumor specimens from five children with; Supratentorial primitive neuroectodermal tumor (sPNET); Pilocytic astrocytoma of the brainstem; Classic medulloblastoma; peripheral primitive neuroectodermal tumor (pPNET) or neuroblastoma (NB), respectively, were transplanted. Analysis of up to 120 sections of each tumor revealed an engraftment for three of the transplanted tumors: pPNET, sPNET, and NB, with a protruding growth from the latter two that were selected for detailed examination. The histology revealed a strict tropism with a non-random integration into what morphologically appeared as matched embryonic microenvironment recuperating the patient tumor histology. The findings suggest specific advantages over xenotransplantation and lead us to propose that transplantation to the human embryonic microenvironment in experimental teratoma can be a well-needed complement for preclinical in vivo studies of childhood neuroectodermal tumors. What's new? The ability to better replicate the human neoplastic niche in vivo could help improve the predictive reliability of animal models. To that end, this study shows that biopsies from childhood neuroectodermal tumors are able to engraft into specific embryonic components of human experimental teratoma. Histological examination revealed a strict tropism of a neuroblastoma as well as a supratentorial primitive neuroectodermal tumor, showing nonrandom integration into morphologically identifiable tissues. The study opens new possibilities for the analysis of growth-promoting environmental factors and for investigating novel therapies targeted to the microenvironment of childhood neuroectodermal tumors.
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| 4. |
- Johansson, Karin
(författare)
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Raising the Costs or Lowering the Bar : International influences on conflict-related sexual violence
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation contributes to the growing literature on conflict-related sexual violence (CRSV). More specifically, the four essays it contains advance our understanding of CRSV by shedding light on the intersection between international involvement and CRSV perpetrated by states and rebel groups engaged in civil war. Despite the increased attention to CRSV among international policy-makers, this intersection has been examined only sparsely within the scholarship on CRSV. Essays I, II, and III address the overarching question of how different types of international involvement influence the level of CRSV. Essay I offers a global study of the effect of third-party military involvement on levels of CRSV. It argues that shifts in the balance of power following external involvement tend to aggravate the situation with regard to CRSV, and it finds indicative support for this. Essay II examines the capacity of peacekeeping missions to mitigate CRSV. It finds that the effectiveness of peacekeeping hinges on the degree of internal control exercised by states and rebel groups. Essay III looks beyond military involvement and focuses on the political power of condemnation. Using newly collected data on condemnations of sexual violence issued by the United Nations (UN) human-rights body between 1987 and 2014, the study tests the extent to which governments that perpetrate CRSV can be influenced by international condemnation. In parallel, the study examines the power of domestic outrage expressed through protests. The findings have important policy implications: Domestic protests are associated with an escalation of CRSV by states. International condemnation correlates with declines in CRSV in recent years (2008–2014), but not historically. International involvement – whether multilateral or unilateral – only materialises if fellow states so decide. Essay IV thus focuses on the willingness of states to take action against CRSV perpetrated by other states. By examining bilateral condemnations of sexual violence issued within the UN Universal Periodic Review, this essay sheds light on the diplomatic relationships and political interests that shape the (un)willingness of individual states to condemn CRSV. In sum, this dissertation makes both theoretical and empirical contributions to the research on CRSV, as well as to the scholarship on international involvement in civil wars more broadly.
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| 5. |
- Nilsson, Stefan, 1972, et al.
(författare)
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Teaching about childhood cancer to pupils aged 10–12 years: A randomised trial of two types of material
- 2019
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Ingår i: British Journal of School Nursing. - 1752-2803. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to describe and compare pupils' experience of teaching about cancer, when a nurse used two different formats of teaching material to teach pupils aged from 10 to 12 years. Pupils from schools in Western Sweden were randomised to either Imaginary Friends or SEE-HEAR-DO pictures. A total of 197 of 231 pupils (85%) participated, and a majority knew someone who had had cancer before, and thought it was valuable to get knowledge about cancer. The Imaginary Friends intervention group felt happier/more content and calmer/more relaxed, and less tense/nervous after the education about cancer. The SEE-HEAR-DO group felt happier/more content after the education, and were to a significantly higher extent stimulated to ask questions. Both Imaginary Friends and SEE-HEAR-DO pictures can be used as teaching materials for pupils. The use of SEE-HEAR-DO pictures may increase the interaction between the school nurse and the pupils.
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| 6. |
- Pollard, K. Michael, et al.
(författare)
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Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN
- 2017
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 199:11, s. 3739-3747
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Tidskriftsartikel (refereegranskat)abstract
- Type I IFN and nucleic acid-sensing TLRs are both strongly implicated in the pathogenesis of lupus, with most patients expressing IFN-induced genes in peripheral blood cells and with TLRs promoting type I IFNs and autoreactive B cells. About a third of systemic lupus erythematosus patients, however, lack the IFN signature, suggesting the possibility of type I IFN-independent mechanisms. In this study, we examined the role of type I IFN and TLR trafficking and signaling in xenobiotic systemic mercury-induced autoimmunity (HgIA). Strikingly, autoantibody production in HgIA was not dependent on the type I IFN receptor even in NZB mice that require type I IFN signaling for spontaneous disease, but was dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton transporter, solute carrier family 15, member 4. HgIA also required the adaptor protein-3 complex, which transports TLRs from the early endosome to the late endolysosomal compartments. Examination of TLR signaling pathways implicated the canonical NF-kappa B pathway and the proinflammatory cytokine IL-6 in autoantibody production, but not IFN regulatory factor 7. These findings identify HgIA as a novel type I IFN-independent model of systemic autoimmunity and implicate TLR-mediated NF-kappa B proinflammatory signaling from the late endocytic pathway compartments in autoantibody generation.
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| 7. |
- Pollard, K. Michael, et al.
(författare)
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Mechanisms of Environment-Induced Autoimmunity
- 2021
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Ingår i: Annual Review of Pharmacology and Toxicology. - : ANNUAL REVIEWS. - 0362-1642 .- 1545-4304. - 9780824304614 ; 61, s. 135-157
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Forskningsöversikt (refereegranskat)abstract
- Although numerous environmental exposures have been suggested as triggers for preclinical autoimmunity, only a few have been confidently linked to autoimmune diseases. For disease-associated exposures, the lung is a common site where chronic exposure results in cellular toxicity, tissue damage, inflammation, and fibrosis. These features are exacerbated by exposures to particulate material, which hampers clearance and degradation, thus facilitating persistent inflammation. Coincident with exposure and resulting pathological processes is the posttranslational modification of self-antigens, which, in concert with the formation of tertiary lymphoid structures containing abundant B cells, is thought to promote the generation of autoantibodies that in some instances demonstrate major histocompatibility complex restriction. Under appropriate gene-environment interactions, these responses can have diagnostic specificity. Greater insight into the molecular and cellular requirements governing this process, especially those that distinguish preclinical autoimmunity from clinical autoimmune disease, may facilitate determination of the significance of environmental exposures in human autoimmune disease.
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| 8. |
- Svensson, Bengt, et al.
(författare)
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Stem Cell Therapy in Injured Vocal Folds : A Three-Month Xenograft Analysis of Human Embryonic Stem Cells
- 2015
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (P <= 0.011). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (P <= 0.031). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives.
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