Objective: To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection.
Methods: HLA class I antigens were immunopurified from a human B-lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell-free SIVmac-32H. Infection was determined by polymerase chain reaction for SIVmac proviral DNA and by virus isolation. Antigen-specific humoral and cellular immune responses were monitored.
Results: Macaques immunized with the HLA molecules produced anti-HLA class I antibodies that inhibited SIV replication in vitro and downregulated autologous T-cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected.
Conclusions: This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.
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CJEM
January 2025
Department of Emergency Medicine, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Objectives: This initiative assessed the integration of the Human Factors Analysis and Classification System, adapted from aviation, into emergency medicine morbidity and mortality rounds. The objective was to determine whether incorporating the Human Factors Analysis and Classification System could lead to a perceived increase in the overall quality of morbidity and mortality presentations through the standardization of classifying cause factors of medical errors.
Methods: This study involved eight emergency medicine residents who applied the adapted Human Factors Analysis and Classification System framework to their morbidity and mortality case presentations over 6 months.
Calcif Tissue Int
January 2025
MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, UK.
Previous studies suggest social support is associated with musculoskeletal health in later life. We explored this relationship further in community-dwelling older adults, by considering associations between different aspects of social support and musculoskeletal health in community-dwelling adults. Participants from the Hertfordshire Cohort Study reported level of confiding/emotional, practical, and negative support using the Close Persons Questionnaire.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Gladstone Institutes, UCSF, San Francisco, CA, USA.
Background: Cerebrovascular alterations and innate immune activation are key features of Alzheimer's disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited.
Method: By developing a multiomic and genetic loss-of-function pipeline, we reported the transcriptomic and global phosphoproteomic landscape of blood-induced microglia activation and the causal role for fibrin in induction of neurodegenerative genes and oxidative stress pathways in innate immune cells.
Int Urogynecol J
January 2025
American Outpatient Medical Center, Department of Internal Medicine, Istanbul, Türkiye.
Introduction And Hypothesis: The objective of our study is to investigate the presence of lower urinary tract symptoms (LUTS) and its correlation with the risk of falling in older women with cognitive frailty.
Methods: The descriptive study was conducted on 102 female older adults, 60 women were classed as cognitively frail and 42 as healthy. Women were classified as having mild cognitive impairment based on the Clinical Dementia Rating Scale and as frail based on the Clinical Frailty Scale.
Alzheimers Dement
December 2024
Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
Background: Although high-throughput DNA/RNA sequencing technologies have generated massive genetic and genomic data in human disease, translation of these findings into new patient treatment has not materialized by lack of effective approaches, such as Artificial Intelligence (AL) and Machine Learning (ML) tools.
Method: To address this problem, we have used AI/ML approaches, Mendelian randomization (MR), and large patient's genetic and functional genomic data to evaluate druggable targets using Alzheimer's disease (AD) as a prototypical example. We utilized the genomic instruments from 9 expression quantitative trait loci (eQTL) and 3 protein quantitative trait loci (pQTL) datasets across five human brain regions from three biobanks.
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