Noninvasive Investigation of Cerebral Ischemia by Phosphorus Nuclear Magnetic Resonance

PEDIATRICS ◽  
1982 ◽  
Vol 70 (2) ◽  
pp. 310-313
Author(s):  
D. T. Delpy ◽  
R. E. Gordon ◽  
P. L. Hope ◽  
D. Parker ◽  
E. O.R. Reynolds ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Human Subjects ◽  
Newborn Infants ◽  
Phosphorus Compounds ◽  
Mobile Phosphorus ◽  
Brain Substance ◽  
The Brain ◽  
Nuclear Magnetic

Brain damage in newborn infants who require intensive care commonly results from cerebral hemorrhage or ischemia leading to infarction.1 Hemorrhages are easy to detect with ultrasound2,3 or computed tomography,4 but neither of these techniques reliably identifies ischemic lesions until loss of brain substance has occurred. Phosphorus (31P) nuclear magnetic resonance (NMR) can be used to measure, noninvasively, the relative concentrations of mobile phosphorus compounds involved in energy metabolism in living systems,5 including the brain of animals in vivo.6,7 Intracellular pH can also be estimated. With the introduction of surface radiofrequency coils6 and topical NMR,8 it has recently become possible to make measurements in human subjects, and these methods are already proving valuable for exploring disorders of muscle (references 9 to 11, and M. J. Dawson, R.H.T. Edwards, R. E. Gordon, et al, unpublished data, 1982).

scholarly journals 4222 Synthesis and application of cyanuric chloride lipids for peptide presentation

2020 ◽  
Vol 4 (s1) ◽  
pp. 17-17
Author(s):  
David Nardo ◽  
Vincent J. Venditto
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Immune Responses ◽  
Human Subjects ◽  
Cyanuric Chloride ◽  
Peptide Epitopes ◽  
Liposomal Formulations ◽  
Peptide Presentation ◽  
Nuclear Magnetic

OBJECTIVES/GOALS: My long-term career objective is to become an established independent researcher focused on understanding and modulating immune responses to biologics in order to enhance their efficacy and understand the underlying mechanisms by which these interact with the immune system. METHODS/STUDY POPULATION: In this study we will evaluate the utility of cyanuric chloride based synthetic lipids in the presentation of peptide epitopes of the gene delivery vector, adeno-associated virus (AAV). The lipopeptide conjugates will be administered to mice via liposomal formulations to assess their ability to induce immune responses by ELISA as compared to mice treated with the AAV. The three-dimensional conformation of the peptides will be evaluated using nuclear magnetic resonance to determine their similarity with the natural conformation that these peptides adapt on the viral surface. Additionally, to assess the translatability of this conjugation strategy, we will test the ability of our lipopeptides to bind to serum antibodies from human subjects. RESULTS/ANTICIPATED RESULTS: We anticipate that peptide presentation using cyanuric chloride lipids will achieve a robust response in mice following immunization. Immunizations with our lipids should induce the production of antibodies targeting AAV, albeit a milder response that the virus itself, given the complexity of viral epitopes. Nuclear magnetic resonance will inform us on how to improve the synthetic lipids to optimize peptide presentation by altering the characteristics of the lipid anchors. Finally, by using human serum to test for the ability of our lipopeptides to bind to antibodies in serum from patients positive for AAV antibodies, we can become informed on whether our strategy has utility in human studies or whether our method is limited to animal models of human disease. DISCUSSION/SIGNIFICANCE OF IMPACT: The current work seeks to develop a strategy to present peptides from a well characterized biologic, AAV, on a liposome surface. Our ultimate purpose is to employ liposomal formulations as decoys that target AAV-specific lymphocytes to improve the in vivo efficacy of AAV.

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