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The diphtheria toxin A chain (DTA) was gene targeted into the Joining chain (J chain) locus to create a mouse strain selecting against J chain-expressing cells, JDTA mice. Serum immunoglobulin (Ig)M and serum IgG were reduced six to eightfold, while serum IgA was elevated 14-fold in these mice. JDTA mice were immune competent although the serum Ig response compared with wild-type mice was reduced
Context:Late-onset hypogonadism (LOH) has been defined as a syndrome in middle-aged and elderly men reporting symptoms in the presence of low testosterone (T). Objective:The objective of the study was to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having LOH according to our previously published criteria. Design, Setting, and Participants:The des
Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is geno
Using a multitissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cof
Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds
Popular Abstract in Swedish Aerob kapacitet, i dagligt tal konditionen, är den maximala förmågan att utföra ett fysiskt arbete karaktäriserat av den maximala syreförbrukningen (V'O2max). Detta maximala arbete kan endast utföras en begränsad tid, till stor del beroende på en tilltagande anaerob metabolism, vilken bl.a. avspeglas som en ökning av utvädrat CO2 i lungorna. Längre tids arbete kan emellDifferent methods are proposed to assess the aerobic capacity. A novel scale, rating of perceived capacity (RPC) based on metabolic equivalents (METs) from 1 to 20, is presented. Selected MET values are linked to physical activities. Comparison of the rating with an exercise test in a group of women revealed that a correction based on age more accurately predicted the maximal exercise capacity. An
Popular Abstract in English This thesis concerns experiments of heat transfer in a rectangular channel with ribs and an obstacle. Liquid crystal thermography (LCT) is used to record the temperature fields in the experiments. LCT is based on measurement of the color response of a heated surface. When illuminated with a white light, the liquid crystals react to temperature changes by changing color,This thesis presents experimental investigations of local heat transfer in a rectangular channel (aspect ratio AR = 4) with continuous transverse ribs as well as an obstacle. Liquid crystal thermography (LCT) is employed to obtain the temperature fields in the heat transfer experiments. The liquid crystal applied here has a red start at 35°C and a bandwidth of 1°C. The work consists of (1) periodi
In recent years, subsets of chronic lymphocytic leukemia (CLL) patients carrying quasi-identical or stereotyped B cell receptors (BcRs) have been identified that share clinicobiological features and disease outcome. While these stereotyped subsets show distinct gene expression and genomic profiles, the DNA methylation landscape remains largely unexplored. By applying high-resolution 450K methylati
Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow-derived T cells do not mediate severe GVHD because of their quantity and/or phenotype. During the course of experiments testing the impact of housing temperatures on GVHD, we discovered
BACKGROUND: Palliative sedation is used to relieve refractory symptoms and is part of clinical practice in Sweden. Yet we do not know how frequently this practice occurs, how decision-making takes place, or even which medications are preferentially used.OBJECTIVES: To understand the current practice of palliative sedation in Sweden.METHODS: We conducted a retrospective cross-sectional medical reco
Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We ex
Osteoarthritis (OA) constitutes a major and increasing burden on patients, health care systems and the broader society. It is estimated that around a quarter of the adult population is affected by OA in the knee and hip and that the prevalence of OA will increase over the coming decades largely due to aging and adverse life-style factors. Prevention and effective care are critical to manage the ch
In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P wa
The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increa
BACKGROUND: The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model.METHODS: To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel
Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility to screen for prostate cancer (PCa). We thus conducted a transcriptome-wide association study (TWAS) of PSA levels using genome-wide summary statistics from 95,768 PCa-free men, the MetaXcan framework, and gene prediction models trained in Genotype-Tissue Expression (GTEx) project data. Tissue-specifi
In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes 1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved 2-4. Here we analyse di
Vaccinated convalescents do not develop severe COVID-19 after infection with new SARS-CoV-2 variants. We questioned how mRNA vaccination of convalescents provides protection from emerging virus variant. From the cohort of 71 convalescent plasma donors, we identified a patient who developed immune response to infection with SARS-CoV-2 variant of 20A clade and who subsequently received mRNA vaccine
BACKGROUND: Cognitive impairment is a serious comorbidity in heart failure patients, but effective therapies are lacking. We investigated the mechanisms that alter hippocampal neurons following myocardial infarction (MI).METHODS: MI was induced in male C57Bl/6 mice by left anterior descending coronary artery ligation. We utilised standard procedures to measure cystic fibrosis transmembrane regulat
OBJECTIVE: To describe the distribution of HIV-1 variants in population-based national surveys conducted in sub-Saharan African countries between 2015 and 2022.DESIGN: Multicountry analysis.METHODS: Sixteen population-based national surveys, conducted between 2015 and 2022, were analyzed. Survey participants were eligible if HIV genotyping was successful. In most countries, people with HIV (PWH) w
