Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

Gangliosides in Nerve Cell Specification.

Abstract: The central nervous system is generated from progenitor cells that are recognized as neural stem cells (NSCs). NSCs are defined as undifferentiated neural cells that are characterized by the capacity for self-renewal and multipotency. Throughout neural development, NSCs undergo proliferation, migration, and cellular differentiation, and dynamic changes are observed in the composition of carbohydrate-rich molecules, including gangliosides. Gangliosides are sialic acid-containing glycosphingolipids with essential and multifaceted functions in brain development and NSC maintenance, which reflects the complexity of brain development. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of ganglioside biosynthesis in NSCs. We found that GD3 is the predominant ganglioside species in NSCs (>80%) and modulates NSC proliferation by interacting with epidermal growth factor receptor signaling. In postnatal brain, GD3 is required for long-term maintenance of NSCs. Deficiency in GD3 leads to developmental and behavioral deficits, such as depression. The synthesis of GD3 is switched to the synthesis of complex, brain-type gangliosides, namely, GM1, GD1a, GD1b, and GT1b, resulting in terminal differentiation and loss of "stemness" of NSCs. In this process, GM1 is augmented by a novel GM1-modulated epigenetic gene regulation mechanism of glycosyltransferases at a later differentiation stage. Consequently, our research suggests that stage-specific gangliosides play specific roles in maintaining NSC activities and in cell fate determination.

Suppression of interactions between prostate tumor cell-surface integrin and endothelial ICAM-1 by simvastatin inhibits micrometastasis.

Abstract: Cancer micrometastasis relies on the ability of cancer cells to secrete angiogenic modulators, to interact with the vascular endothelium, and to overcome the resistance offered by the endothelial-barrier. Being an essential step prior to metastasis, blockage of micrometastasis can have potential applications in cancer therapy and metastasis prevention. Due to poorly known molecular mechanisms leading to micrometastasis, developing therapeutic strategies to target prostate cancer utilizing drugs that block micrometastasis is far from reality. Here, we demonstrate the potential benefits of simvastatin in the inhibition of prostate cancer micrometastasis and reveal the novel molecular mechanisms underlying this process. First, we showed that simvastatin inhibited the ability of human PC3 prostate cancer cells for transendothelial migration in vitro. Second, our data indicated that simvastatin modulates the expression of tumor-derived factors such as angiopoietins and VEGF-A at the mRNA and protein levels by the PC3 cells, thus preventing endothelial-barrier disruption. Third, simvastatin directly activated endothelial cells and enhances endothelial-barrier resistance. Apart from this, our study revealed that simvastatin-mediated effect on PC3 micrometastasis was mediated through inhibition of integrin αv β3 activity and suppression of interaction between prostate cancer cell integrin αv β3 with endothelial ICAM-1.

PRKCD/PKCδ contributes to nephrotoxicity during cisplatin chemotherapy by suppressing autophagy.

Abstract: Nephrotoxicity is a major side effect during chemotherapy with cisplatin and related platinum compounds. Previous work unveiled a role of PRKCD/PKCδ (protein kinase C delta) in cisplatin-induced nephrotoxicity; however, the underlying mechanism was largely unknown. Our recent work showed that PRKCD may suppress macroautophagy/autophagy, a cytoprotective mechanism, to promote kidney tubule cell death during cisplatin treatment. Interestingly, PRKCD may do so by phosphorylating AKT, which further phosphorylates MTOR to repress ULK1.

The incidental finding of a persistent left superior vena cava: implications for primary care providers-case and review.

Abstract: Persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly and is a persistent congenital remnant of the vena caval system from early cardiac development. Patients with congenital anomalous venous return are at increased risk of developing various cardiac arrhythmias, due to derangement of embryologic conductive tissue during the early development of the heart. Previously this discovery was commonly made during the placement of pacemakers or defibrillators for the treatment of the arrhythmias, when the operator encountered difficulty with proper lead deployment. However, in today's world of various easily obtainable imaging modalities, PLSVC is being discovered more and more by primary care providers during routine testing or screening for other ailments. Given the known association between anomalous venous return and the propensity for cardiac arrhythmias, we review the embryology of PLSVC and the mechanisms by which it leads to conduction abnormalities. We also provide the practitioner with recommendations for certain baseline cardiac observations and suggestions for proper surveillance in hopes that better understanding will reduce unnecessary and potentially harmful testing, premature subspecialty referral, and unneeded patient anxiety.