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Diagnostic and Therapeutic Uses of Augmenter of Liver Regeneration (ALR) in Inflammatory Conditions

详细技术说明

None

*Abstract

This invention relates to the diagnostic detection and/or suppression of Augmenter of Liver Regeneration (ALR) in settings of acute inflammation such as sepsis or trauma/hemorrhage. ALR (Augmenter of Liver Regeneration, originally named hepatic stimulatory substance) was identified in the cytosolic fraction of residual liver fragments following 70% hepatectomy and in weanling animal livers. An antibody to ALR was developed by Drs. Starzl and Gandhi, and this antibody serves as the basis for an enzyme-linked immunosorbent assay (ELISA). Using this antibody for immunohistochemical and Western blot studies, Dr. Gandhi demonstrated that ALR is present in large amounts in the unmodified adult rat liver. These results contrast the previous belief that ALR is present only in hyperplastic livers, and prompted the hypothesis that ALR may exert other functions in a normal liver. Thus, ALR appears to be an early, alarm-phase cytokine that modulates inflammation and cell death. Therefore, detection of circulating ALR may serve a diagnostic purpose in inflammatory diseases. Similarly, modulation of ALR may have therapeutic applications.Applications:1) detection of ALR as an early diagnostic of acute inflammation, for example in sepsis or trauma, using the ALR-specific ELISA2) inhibition of ALR bioactivity, through neutralization, inhibition of receptor binding, or modulation of post-receptor intracellular signaling.Advantages:1) ALR levels are elevated more rapidly and more persistently than other known inflammatory markers in sepsis and other inflammatory disorders.2) Early detection of ALR may indicate the severity of sepsis, and the persistence may allow for a larger therapeutic window.Provisional Patent Application Filed

*Principal Investigation

Name: Chandrashekhar Gandhi, Associate Professor

Department: Med-Surgery

Name: Thomas Starzl

Department: Med-Surgery

Name: Yoram Vodovotz, Associate Professor of Surgery

Department: Med-Surgery

国家/地区

美国