Seroconversion of red blood cell antibody in ABO-incompatible living donor liver transplantation-a case report- / 대한마취과학회지

Background@#; Liver transplantation usually requires blood transfusion, and a red blood cell (RBC) antibody screen is essential for the prevention of a hemolytic reaction. Since proper ABO-compatible grafts are lacking, ABO-incompatible living donor liver transplantation (ABO-i LDLT) with desensitization is a feasible therapy. Desensitization includes intravenous rituximab injection and plasmapheresis before surgery.Case: A 60-year-old female was diagnosed with hepatitis B virus-related hepatocellular carcinoma and planned for ABO-i LDLT. She tested positive in a RBC antibody screen over two years; however, she tested negative for the test after desensitization. Clinicians noted the seroconversion during induction, and thus, a delay in the preparation of adequate packed RBC was unavoidable. @*Conclusions@#Even when the latest RBC antibody screen is negative after immunosuppression, clinicians should consider the possibility of a prior positive result to promote safer medical treatment and management.

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells

BACKGROUND: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. METHODS: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 microM) of deferoxamine (DFO) and H2O2. RESULTS: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3alpha (GSK3alpha) and beta corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3alpha and beta also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. CONCLUSION: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.