Microglia are the primary immune cell of the CNS, comprising 5–20% of the ∼60 billion neuroglia in the human brain. In the developing and adult CNS, they preferentially target active neurons to guide synapse maturation and remodeling. At the same time, they are the first line of defense against bacterial, fungal, and viral CNS infections. Although an extensive literature details their roles in rodents, less is known about how they function in humans because of the difficulty in obtaining tissue samples and the understandable inability to extensively study human microglia in situ. In this study, we use recent advances in the study of brain microenvironments to establish cultures of primary human microglia in a serum-free medium. Postsurgical samples of human brain were enzymatically and mechanically dissociated into single cells, and microglia were isolated at high purity by positive selection using CD11b Ab–coated microbeads. The CD11b+ cells were plated on poly-l-lysine–coated surfaces and bathed in serum-free DMEM/F12 supplemented with three essential components (TGF-β, IL-34, and cholesterol). Under these conditions, microglia assumed a ramified morphology, showed limited proliferation, actively surveyed their surroundings, and phagocytosed bacterial microparticles. In the presence of LPS, they assumed a more compact shape and began production of proinflammatory cytokines and reactive oxygen species. LPS on its own triggered release of TNF-α, whereas release of IL-1β required costimulation by ATP. Thus, human microglia maintained in a defined medium replicate many of the characteristics expected of native cells in the brain and provide an accessible preparation for investigations of human microglial physiology, pharmacology, and pathophysiology.
Contrast enhanced magnetic resonance angiography (CE-MRA) is limited by long acquisition time and contrast exposure in aortic emergencies. To compare the effcacy of dark blood (DB) and bright blood (BB) noncontrast sequences with the gold standard CE-MRA using a novel protocol for performing consistent thoracic aortic measurements and thoracic aortic pathologies identifications. A total of 66 patients with suspected or known thoracic aortic pathology who underwent CE-MRA underwent DB and BB imaging prior to CE-MRA for planning purposes. Aortic dimension was measured at 10 standard reference points in the ascending, arch, and descending aorta. Detection of aortic pathologies was recorded individually for each noncontrast sequence. When comparing the CE-MRA to the DB images and CE-MRA to the BB images, a majority of the measurement differences were less than or equal to 2 mm or resulted in no change of diagnostic class (95% for CE-MRA vs. DB and 96% for CE-MRA vs. BB). Of the patients who had major changes in diagnostic class (e.g., changes in two or three classes), the absolute measurements were not clinically significant in any given patient to warrant a change in management. Individually, the DB and BB sequences allowed for accurate recognition of all 47 aortic pathologies. DB and BB sequences produced comparable and consistent measurements of the thoracic aorta when compared with CE-MRA. In a situation where CE-MRA is not readily available or contraindicated, noncontrast MRA using our protocol is a reliable alternative to CE-MRA for assessment of aortic pathologies.
Summary We identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin. Learning points HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history. Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes. First-degree relatives of the affected individual should be considered for genetic testing. The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.
No abstract
No abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.