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| 2. |
- af Edholm, Karolina, et al.
(author)
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Clinical Reasoning : Leg weakness and stiffness at the emergency room
- 2019
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In: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 92:6, s. E622-E625
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Journal article (other academic/artistic)abstract
- A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.
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| 3. |
- Jansson, Kaj, 1987-, et al.
(author)
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Simulated production rates of exotic nuclei from the ion guide for neutron-induced fission at IGISOL
- 2017
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In: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 53:12
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Journal article (peer-reviewed)abstract
- An investigation of the stopping efficiency of fission products, in the new ion guide designed for ion production through neutron-induced fission at IGISOL in Jyväskylä, Finland, has been conducted. Our simulations take into account the new neutron converter, enabling measurements of neutron-induced fission yields, and thereby provide estimates of the obtained yields as a function of primary proton beam current. Different geometries, targets, and pressures, as well as models for the effective charge of the stopped ions were tested, and optimisations to the setup for higher yields are suggested. The predicted number of ions stopped in the gas lets us estimate the survival probability of the ions reaching the downstream measurements stations.
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| 4. |
- Kaipe, Helen, et al.
(author)
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MAIT Cells at the Fetal-Maternal Interface During Pregnancy
- 2020
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In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Research review (peer-reviewed)abstract
- One of the main functions of the human placenta is to provide a barrier between the fetal and maternal blood circulations, where gas exchange and transfer of nutrients to the developing fetus take place. Despite being a barrier, there is a multitude of crosstalk between maternal immune cells and fetally derived semi-allogeneic trophoblast cells. Therefore, the maternal immune system has a difficult task to both tolerate the fetus but at the same time also defend the mother and the fetus from infections. Mucosal-associated invariant T (MAIT) cells are an increasingly recognized subset of T cells with anti-microbial functions that get activated in the context of non-polymorphic MR1 molecules, but also in response to inflammation. MAIT cells accumulate at term pregnancy in the maternal blood that flows into the intervillous space inside the placenta. Chemotactic factors produced by the placenta may be involved in recruiting and retaining particular immune cell subsets, including MAIT cells. In this Mini-Review, we describe what is known about MAIT cells during pregnancy and discuss the potential biological functions of MAIT cells at the fetal-maternal interface. Since MAIT cells have anti-microbial and tissue-repairing functions, but lack alloantigen reactivity, they could play an important role in protecting the fetus from bacterial infections and maintaining tissue homeostasis without risks of mediating harmful responses toward semi-allogenic fetal tissues.
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| 7. |
- Solders, Andreas, 1976-, et al.
(author)
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Simulations of the stopping efficiencies of fission ion guides
- 2017
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In: Nd 2016. - Les Ulis : EDP Sciences. - 9782759890200
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Conference paper (peer-reviewed)abstract
- With the Ion Guide Isotope Separator On-Line (IGISOL) facility, located at the University of Jyväskylä, products of nuclear reactions are separated by mass. The high resolving power of the JYFLTRAP Penning trap, with full separation of individual nuclides, capacitates the study of nuclides far from the line of stability. For the production of neutron-rich medium-heavy nuclides, fissioning of actinides is a feasible reaction. This can be achieved with protons from an in-house accelerator or, alternatively, with neutrons through the addition of a newly developed Be(p,xn)-converter. The hereby-obtained fission products are used in nuclear data measurements, for example fission yields, nuclear masses, Q-values and decay spectroscopy. Prior to separation, the ionized reaction products are stopped in a helium-filled gas cell, referred to as the ion-guide. In this work we present simulations of the stopping of fission products in an ion guide developed for neutron-induced fission. The production and extraction rates are evaluated and compared against experimental values.
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| 8. |
- Solders, Martin
(author)
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MAIT cells in placental tissues and their reconstitution following allogeneic hematopoietic stem cell transplantation
- 2020
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Doctoral thesis (other academic/artistic)abstract
- The placenta is a temporary organ of human reproduction. Both the fetus and placenta are covered in a membrane of maternal origin, the decidua. After the 1st trimester, the fetus is supplied with oxygen and nutrients by maternal arterial blood that penetrates the decidua and fills the intervillous space of the placenta. Fetal blood vessels covered in a thin cell layer, the villi, protrude down into this intervillous blood (IVB), and gases and molecules are transported in and out of the fetal circulation. The maternal immune system recognizes fetal antigen as foreign, yet in the case of a successful pregnancy, it tolerates the fetus while still maintaining immunity against pathogens. Maternal immune cells come into contact with fetal antigen in the decidua and the intervillous space, and these immunological sites are referred to as the feto-maternal interface. Mucosal associated invariant T (MAIT) cells is a large subset of antigen-specific T cells. MAIT cells are activated by metabolites from the synthesis of vitamin B2 by certain species of bacteria and fungi, which are presented on the MHC class I related molecule (MR1). As humans cannot synthesize vitamin B2, MAIT cells can thus discern between self and non-self. In this thesis, we have studied the immune cell composition and function at the feto-maternal interface with special focus on MAIT cells. We also studied the reconstitution of MAIT cells in the conceptually interesting context of allogeneic hematopoietic cell transplantation (HCT). We found that IVB has a fundamentally different composition of immune cells compared to peripheral blood (PB) from the same donors. The IVB was enriched in MAIT cells, effector memory T cells and B cells. The MAIT cells in IVB had a more potent response when stimulating mixed mononuclear cell cultures with bacteria compared to PB. MR1 was readily expressed by fetal macrophages inside the villi. We compared immune cells isolated from the two different parts of the decidual membrane, the decidua basalis (DB) that covers the placenta from the maternal side, and the decidua parietalis (DP) that is attached to the edge of the placenta, and covers the fetus and amniotic fluid. DP contained more T cells and CD56high NK cells, whereas DB was enriched in MAIT cells, B cells, monocytes and CD56dim NK cells. Immune cells in DP had a higher expression of co-inhibitory markers such as PD-1, TIM-3 and LAG-3. In spite of this expression, MAIT cells, T cells and NK cells from both DP and DB were functional when stimulated with bacteria or PMA/Ionomycin. Non-pregnant women had a higher frequency of MAIT cells in PB compared to pregnant women at term. Using supernatants from placenta tissue explant cultures, we observed that MAIT cells and CD8+ effector T cells were selectively recruited in migration assays. When analyzing the chemokine and cytokine patterns in these supernatants and plasma samples from IVB, many similarities were seen. In contrast, the levels of chemokines in PB plasma was strikingly different compared to that of IVB plasma. Among these, macrophage migration inhibitory factor (MIF) was 182-fold higher in IVB compared to PB plasma. The frequency of MAIT cells in both IVB and DP correlated with levels of MIF in IVB. When blocking MIF together with CCL20 and CCL25, the migration of MAIT cells towards the placenta tissue explant supernatant was reduced. Using recombinant MIF protein, we could show that MIF attracted MAIT cells, probably by binding the chemokine receptor CXCR4. IVB contained a higher proportion of B cells compared to PB, and the IVB B cells were primarily of the mature/naïve phenotype. This subset of B cells was correlated with levels of CCL20 in IVB plasma. Mature/naïve B cells all expressed the receptor for CCL20, CCR6, and they had a higher median fluorescent intensity of CCR6 compared to immature B cells. Using the same migration assay as previously, we could see that placenta tissue explant supernatant attracted B cells. Lastly, we investigated the reconstitution of MAIT cells following HCT. MAIT cells did not start to increase in total number until two years after the transplantation, and as the non-MAIT T cells proliferated during this time, the relative proportion of MAIT cells remained at the same low levels during the observation period. When stimulating mixed mononuclear cells with bacteria, the MAIT cells from 2-6 months after HCT had an impaired interferon-γ response, whereas the response at 24 months was similar to that seen in healthy controls. Lastly, we showed that proliferating MAIT cells were more sensitive to common immunosuppressive drugs used in patients after HCT. In conclusion, the immunological constitution and function of IVB seems to be shaped by soluble factors secreted by placental tissue. IVB is a specialized immunological environment enriched in MAIT cells and other effector T cells, as well as mature B cells, and challenging IVB mononuclear cells with bacteria led to a more potent MAIT cell response. This points to that the placenta attracts certain subsets of immune cells in order to uphold immunity at the feto-maternal interface. MAIT cell reconstitution following HCT was impaired, both in terms of cell number, frequency and function. This could partly be explained by an increased sensitivity of dividing MAIT cells to common immunosuppressive drugs used after transplantation. The impaired MAIT cell reconstitution could partly be an explanation of the increased risk of infectious complications following HCT
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| 9. |
- Solders, Martin, et al.
(author)
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Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis
- 2017
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In: Stem Cells International. - : Hindawi Limited. - 1687-9678 .- 1687-966X. ; 2017
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Journal article (peer-reviewed)abstract
- © 2017 Martin Solders et al. The maternal part of the placenta, the decidua, consists of maternal immune cells, decidual stromal cells, and extravillous fetal trophoblasts. In a successful pregnancy, these cell compartments interact to provide an intricate balance between fetal tolerance and antimicrobial defense. These processes are still poorly characterized in the two anatomically different decidual tissues, basalis and parietalis. We examined immune cells from decidua basalis and parietalis from term placentas (n=15) with flow cytometry. By using multivariate discriminant analysis, we found a clear separation between the two decidual compartments based on the 81 investigated parameters. Decidua parietalis lymphocytes displayed a more activated phenotype with a higher expression of coinhibitory markers than those isolated from basalis and contained higher frequencies of T regulatory cells. Decidua basalis contained higher proportions of monocytes, B cells, and mucosal-associated invariant T (MAIT) cells. The basalis B cells were more immature, and parietalis MAIT cells showed a more activated phenotype. Conventional T cells, NK cells, and MAIT cells from both compartments potently responded with the production of interferon-γ and/or cytotoxic molecules in response to stimulation. To conclude, leukocytes in decidua basalis and parietalis displayed remarkable phenotypic disparities, indicating that the corresponding stromal microenvironments provide different immunoregulatory signals.
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| 10. |
- Stikvoort, Arwen, et al.
(author)
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Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition
- 2018
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In: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 24:3, s. 467-477
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Journal article (peer-reviewed)abstract
- Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post-hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-a (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-a levels in both graft and patient before HSCT in development of aGVHD.
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