Dr. Björn Ekwall (1940-2000) was an outstanding Swedish cell toxicologist who made pioneering contributions to the field of in vitro toxicology. In particular, he formulated the so called "basal cytotoxicity concept" (1983) which provided a conceptual basis for the estimation of acute systemic toxicity of chemicals in humans by the use of in vitro tests. Björn Ekwall formulated, initiated and, together with a group of dedicated Scandinavian toxicologists, guided the MEIC project (Multicentre Evaluation of In Vitro Cytotoxicity Programme, 1989-1999), in which 50 reference chemicals were voluntary tested in 100 laboratories worldwide by 61 different in vitro assays. This project was unique because human sub-lethal and lethal blood concentrations were used for a first time as a reference system for the evaluation of predictability of in vitro tests for human acute systemic toxicity. The results of MEIC project have shown good correlation between human LC₅₀ values (50% lethal concentrations) and IC₅₀ values (50% inhibitory concentrations from basal cytotoxicity tests), by the use a battery of three 24-h basal cytotoxicity tests (R²=0.77). The MEIC project paved the way to the present validation projects, under EU 6th Framework programme, such as ACuteTox, Sens-it-iv, and ReProTect.
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http://dx.doi.org/10.1016/j.tiv.2010.04.004 | DOI Listing |
J Clin Immunol
December 2024
Department of Immunology, Royal Free London NHS Foundation Trust, London, UK.
Purpose: Significant improvements in the prognosis for young patients with Primary Immunodeficiency Diseases (PID) and Autoinflammatory Disorders (AID), which together make up the majority of Inborn Errors of Immunity (IEI), have resulted in the need for optimisation of transition and transfer of care to adult services. Effective transition is crucial to improve health outcomes and treatment compliance among patients. Evaluations of existing transition programmes in European health centres identified the absence of disease-specific transition guidelines for PID and AID, as a challenge to the transition process.
View Article and Find Full Text PDFNat Commun
December 2024
Crown Princess Victoria Children's Hospital, and Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Females exhibit a more robust immune response to both self-antigens and non-self-antigens than males, resulting in a higher prevalence of autoimmune diseases but more effective responses against infection. Increased expression of X-linked immune genes in female T cells is thought to underlie this enhanced response. Here we isolate thymocytes from pediatric thymi of healthy males (46, XY), females (46, XX), a female with completely skewed X-chromosome inactivation (46, XX, cXCI) and a female with Turner syndrome (45, X0).
View Article and Find Full Text PDFEpigenomes
October 2024
Department of Medicine Huddinge, Division of Biosciences and Nutrition, Karolinska Institute, NEO Building, SE-141-83 Huddinge, Sweden.
(1) Background: Quiescent cells are those that have stopped dividing and show strongly reduced levels of gene expression during dormancy. In response to appropriate signals, the cells can wake up and start growing again. Many histone modifications are regulated in quiescence, but their exact functions remain to be determined.
View Article and Find Full Text PDFArthritis Res Ther
October 2024
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Background: Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.
View Article and Find Full Text PDFClin Transl Immunology
October 2024
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden.
Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL.
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