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Sökning: LAR1:gu > Lunds universitet

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51.
  • Alattar, Abdul Ghani, et al. (författare)
  • Recombinant alpha(1)-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-177-DOTATATE Mouse Radiation Model
  • 2023
  • Ingår i: Biomolecules. - 2218-273X. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-177-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. alpha (1)-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse Lu-177-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post-Lu-177-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with Lu-177-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with Lu-177-DOTATATE.
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52.
  • Albert, J., et al. (författare)
  • Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
  • 2014
  • Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
  • Tidskriftsartikel (refereegranskat)abstract
    • The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
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53.
  • Albinsson, Bo, et al. (författare)
  • Seroprevalence of tick-borne encephalitis virus and vaccination coverage of tick-borne encephalitis, Sweden, 2018 to 2019
  • 2024
  • Ingår i: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. - 1560-7917. ; 29:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn Sweden, information on seroprevalence of tick-borne encephalitis virus (TBEV) in the population, including vaccination coverage and infection, is scattered. This is largely due to the absence of a national tick-borne encephalitis (TBE) vaccination registry, scarcity of previous serological studies and use of serological methods not distinguishing between antibodies induced by vaccination and infection. Furthermore, the number of notified TBE cases in Sweden has continued to increase in recent years despite increased vaccination.AimThe aim was to estimate the TBEV seroprevalence in Sweden.MethodsIn 2018 and 2019, 2,700 serum samples from blood donors in nine Swedish regions were analysed using a serological method that can distinguish antibodies induced by vaccination from antibodies elicited by infection. The regions were chosen to reflect differences in notified TBE incidence.ResultsThe overall seroprevalence varied from 9.7% (95% confidence interval (CI): 6.6-13.6%) to 64.0% (95% CI: 58.3-69.4%) between regions. The proportion of vaccinated individuals ranged from 8.7% (95% CI: 5.8-12.6) to 57.0% (95% CI: 51.2-62.6) and of infected from 1.0% (95% CI: 0.2-3.0) to 7.0% (95% CI: 4.5-10.7). Thus, more than 160,000 and 1,600,000 individuals could have been infected by TBEV and vaccinated against TBE, respectively. The mean manifestation index was 3.1%.ConclusionA difference was observed between low- and high-incidence TBE regions, on the overall TBEV seroprevalence and when separated into vaccinated and infected individuals. The estimated incidence and manifestation index argue that a large proportion of TBEV infections are not diagnosed.
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54.
  • Albrecht, F., et al. (författare)
  • Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data
  • 2022
  • Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 102, s. 19-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. Methods: Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. Results: Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. Conclusions: Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.
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55.
  • Albrekt, Ann-Sofie, et al. (författare)
  • Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency
  • 2014
  • Ingår i: Bmc Pharmacology & Toxicology. - : Springer Science and Business Media LLC. - 1471-2210 .- 2050-6511. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Methods: Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. Results: By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. Conclusions: This study demonstrates that functional analysis of biomarkers identified from our genomics study of human MUTZ-3 cells can be used to assess sensitizing potency of chemicals in vitro, by the identification of key cellular events, such as metabolic and cell cycling pathways.
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56.
  • Aldman, Malin Hagstrand, et al. (författare)
  • Endocarditis due to Staphylococcus lugdunensis-a retrospective national registry-based study
  • 2021
  • Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 40
  • Tidskriftsartikel (refereegranskat)abstract
    • We present characteristics of infective endocarditis (IE) caused by Staphylococcus lugdunensis and compare with IE caused by Staphylococcus aureus and other CoNS, in the National Swedish Registry of IE (2008-2018). Thirty episodes of S. lugdunensis IE were registered, of which 21 cases affected native valves, and 7 patients were subjected to surgery. The mortality rate at 30 days was significantly higher for S. lugdunensis IE (20%, n = 6), than for IE caused by other CoNS (7%) or S. aureus (9%) p = 0.016. Septic embolisation was only reported in two cases (7%). The most common treatment was isoxazolyl penicillin (n = 18).
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57.
  • Aldridge, Jonathan, et al. (författare)
  • Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients
  • 2018
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD-and corticosteroid-naive patients (50 females and 22 males) and in 31 healthy age-and sex-matched controls. Broad analysis of helper and regulatory CD4(+) T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR. Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4(+) T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA. Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
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58.
  • Alhadad, Alaa, et al. (författare)
  • Renal angioplasty causes a rapid transient increase in inflammatory biomarkers, but reduced levels of interleukin-6 and endothelin-1 1 month after intervention.
  • 2007
  • Ingår i: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 25:9, s. 1907-14
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To examine prospectively whether inflammatory biomarkers and endothelin (ET)-1 are increased in patients with renal artery stenosis (RAS), and to investigate how treatment with percutaneous transluminal renal angioplasty (PTRA) affects these variables during the first month after intervention. METHODS: One hundred patients with suspected RAS undergoing renal angiography were included. PTRA was performed if the trans-stenotic mean arterial pressure gradient was>or=10 mmHg. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), neopterin, CD40 ligand (CD40L) and endothelin-1 (ET-1) were measured before, and 1 day and 1 month after PTRA (n=61) or diagnostic angiography only (n=39). RESULTS: At baseline there were no significant differences in inflammatory biomarkers or ET-1 levels between patients subsequently undergoing PTRA or angiography only. After angiography, IL-6 and hs-CRP had increased in both groups compared to baseline (P<0.001). At this time point hs-CRP (10.90+/-1.48 versus 6.37+/-1.61 mg/l; P<0.05) and IL-6 (13.70+/-0.94 versus 13.00+/-0.17 pg/ml; P<0.01) were higher in the PTRA group than in patients subjected to angiography only. One month after PTRA, systolic blood pressure and levels of IL-6 and ET-1 were lower than before intervention (P<0.05), whereas CD40L had increased compared to baseline (P<0.01). CONCLUSION: In patients with RAS, PTRA triggers rapid transient increases in hs-CRP and IL-6; however, 1 month after PTRA, both IL-6 and ET-1 had decreased compared to before intervention, indicating beneficial effects of PTRA on inflammation and the endothelin system.
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59.
  • Ali, Abdulemir, et al. (författare)
  • Dissatisfied patients after total knee arthroplasty
  • 2014
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:3, s. 229-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose - In 2003, an enquiry by the Swedish Knee Arthroplasty Register (SKAR) 2-7 years after total knee arthroplasty (TKA) revealed patients who were dissatisfied with the outcome of their surgery but who had not been revised. 6 years later, we examined the dissatisfied patients in one Swedish county and a matched group of very satisfied patients. Patients and methods - 118 TKAs in 114 patients, all of whom had had their surgery between 1996 and 2001, were examined in 2009-2010. 55 patients (with 58 TKAs) had stated in 2003 that they were dissatisfied with their knees and 59 (with 60 TKAs) had stated that they were very satisfied with their knees. The patients were examined clinically and radiographically, and performed functional tests consisting of the 6-minute walk and chair-stand test. All the patients filled out a visual analog scale (VAS, 0-100 mm) regarding knee pain and also the Hospital and Anxiety and Depression scale (HAD). Results - Mean VAS score for knee pain differed by 30 mm in favor of the very satisfied group (p < 0.001). 23 of the 55 patients in the dissatisfied group and 6 of 59 patients in the very satisfied group suffered from anxiety and/or depression (p = 0.001). Mean range of motion was 11 degrees better in the very satisfied group (p < 0.001). The groups were similar with regard to clinical examination, physical performance testing, and radiography. Interpretation - The patients who reported poor response after TKA continued to be unhappy after 8-13 years, as demonstrated by VAS pain and HAD, despite the absence of a discernible objective reason for revision.
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60.
  • Ali, A., et al. (författare)
  • Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells
  • 2022
  • Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Metformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous. Methods: MF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency. Results: MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1α proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity. Conclusions: These findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.
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