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.

The Moderating Effect of Religious Involvement on the Relationship Between PTSD Symptoms and Physical Pain in U.S. Veterans and Active Duty Military

Abstract: The relationship between posttraumatic stress disorder (PTSD) symptom severity and pain is well known in veterans and active duty military (V/ADM). This study examines the buffering effect of relig...

IRF8 deficiency in colonic epithelial cells promotes inflammation-mediated colon tumorigenesis and myeloid-derived suppressor cell differentiation.

Abstract: IRF8 is a member of the nine IRF family proteins that was originally identified as a key transcription factor for myeloid cell lineage differentiation IRF8 deficiency leads to deregulation of myelopoiesis and accumulation of CD11b + Gr1 + immature myeloid cells that phenotypically and functionally resemble tumor-induced myeloid-derived suppressor cells (MDSCs) It has since been documented that IRF8 also plays important roles in other immune cells, including B, Natural Killer, Dendritic and T cells IRF8 expression and function has recently been extended to non-hematopoietic cells, including epithelial cancer cells and heart cells IRF8 is often silenced by its promoter DNA methylation in cancer cells However, low level of IRF8 is expressed in cancer cells and IRF8 is IFNg inducible in cancer cells IRF8 acts as an apoptosis inducer To determine the function of IRF8 in spontaneous tumor development, we generate IRF8 deficient mice with IRF8 KO only in colonic epithelial cells (termed IRF8 CKO mice) Unlike conventional IRF8-deficient mice, IRF8 CKO mice phenotypically resemble WT mice However, IRF8 CKO exhibited greater susceptibility to AOM-DSS-induced colon cancer formation as compared to WT mice Although no differences were observed in MDSC profiles between WT and IRF8 CKO mice, tumor-bearing IRF8 CKO mice have significantly higher level of CD11b + Gr1 + MDSCs than tumor-bearing WT mice Our data determine that IRF8 functions in colonic epithelial cells as a spontaneous colon cancer suppressor and also functions in colon carcinoma cells to mediate MDSC differentiation in tumor-bearing host in vivo

Phosphorylation by GSK-3β increases the stability of SIRT6 to alleviate TGF-β-induced fibrotic response in renal tubular cells

Abstract: The deacetylase Sirtuin 6 (SIRT6) is up-regulated during fibrogenesis in renal tubular cells and post-ischemia/reperfusion kidneys. Hence, our aim was to investigate the mechanism of SIRT6 up-regulation upon profibrotic stress.Immunohistochemical staining was used to detect the expression of UBC9 in the kidney section. The interaction of GSK-3β and SIRT6, and phosphorylation level of SIRT6 were detected by the immunoprecipitation assay. The wild-type and phosphorylated site mutant plasmids of SIRT6 were constructed and stably transfected to BUMPT cells to evaluate the phosphorylation function of SIRT6 by immunoblotting assay.The phosphorylation of SIRT6 is significantly increased during TGF-β treatment in mouse renal tubular cells. GSK-3β can physically interact with SIRT6 in renal tubular cells, and this interaction is enhanced by TGF-β treatment. Moreover, GSK-3β is the phosphorylation kinase for SIRT6, and phosphorylates SIRT6 at Serine 326 residue to prevent its ubiquitination-mediated proteasomal degradation. Non-phosphorylatable mutant, S326A, of SIRT6, restores β-catenin activation and fibrotic changes in renal tubular cells.The present study demonstrates that a new mechanism for GSK-3β-mediated anti-fibrotic function in renal fibrosis through phosphorylation of SIRT6 to prevent its proteasomal degradation.

Acute Esophageal Necrosis Resulting in Esophageal Perforation

Abstract: Acute esophageal necrosis (AEN), also commonly referred to as “black esophagus,” is a rare clinical entity characterized by circumferential black necrosis of esophageal mucosa at various lengths but typically involving the distal esophagus with marked abruption to normal mucosa at the gastroesophageal (GE) junction. Patients typically present with the symptoms of an upper gastrointestinal (GI) hemorrhage, and the diagnosis is made on subsequent esophagogastroduodenoscopy (EGD) once other causes of acute esophagitis, such as radiation, trauma, infection, and caustic ingestion, have been excluded.1 The prevalence of AEN is approximately 0.2 per cent of those undergoing EGD, and there appears to be a 4:1 male predominance.1 Although the etiology of AEN is not clear, it is thought to be related to a low perfusion state and subsequent mucosal injury secondary to numerous possible conditions such as esophageal reflux, sepsis, vasculopathy, diabetic ketoacidosis, alcohol intoxication, and more.1, 2 The disease course of AEN is typically transient in nature, and treatment largely revolves around supportive therapy with medical management alone. In approximately 7 per cent of cases, however, esophageal perforation can occur which requires prompt surgical evaluation and operative management.2 Herein, we describe a case in which a 63-year-old male is diagnosed with AEN complicated by perforation, a rare complication of AEN necessitating surgical intervention. Our patient is a 63-year-old male who was admitted to the ICU for sepsis and complaints of chest pain. He reported a prior hospitalization for esophagitis and had a history of heavy alcohol use. As part of his workup, an EGD was performed which revealed diffuse black esophagus from 20 cm to the GE junction with marked transition to normal gastric mucosa, suggestive of AEN (Fig. 1). In addition, our patient was noted to have a duodenal ulcer on EGD. He was treated with medical management, including intravenous proton pump inhibitors and fluid resuscitation; however, his condition worsened and a CT thorax was performed which revealed an esophageal perforation near the GE junction (Fig. 2). The patient was taken to the operating room where a subtotal esophagectomy, esophagostomy, and gastrostomy tube placement were performed via a laparotomy, right thoracotomy, and left cervical dissection (three-incision esophagectomy). Intraoperatively, the patient was noted to have extensive full thickness necrosis of the middle and distal esophagus. The necrotic tissue was successfully excised; however, primary reconstruction was avoided because of the patient’s critical state and friable tissue. The patient’s postoperative course was unremarkable, and delayed reconstruction is anticipated in the future. Despite the rarity of AEN, the condition is thought to be more common than described in the literature because of the transient nature of the disease, and thus, it remains an important consideration in the setting of upper GI bleeding.2 The diagnosis is largely one of exclusion, with specific diagnostic criteria as defined by Moreto et al.,3 including 1) absence of caustic ingestion, 2) diffusely black esophagus with or without exudates, 3) preferential involvement of the distal third of the esophagus with marked transition to normal mucosa at the transitional line, and 4) histology consistent with necrosis. Biopsies demonstrating necrosis help differentiate the condition from other possible diagnoses, such as melanosis, acanthosis nigricans, and coal dust deposition.2 Several risk factors for the development of AEN have been identified and include advanced age, male gender, renal insufficiency, hypoxemia, hypercoagulable disorders, trauma, alcohol use, gastric outlet obstruction, and hemodynamic compromise.4 The overall prognosis is generally poor, with mortality rates ranging from 12.5 to 38 per cent.1, 2, 4 Despite this, deaths attributed to AEN alone are significantly Address correspondence and reprint requests to Andrew Harner, M.D., Augusta University Medical College of Georgia, 1120 15th Street, Augusta, GA 30912. E-mail: aharner@augusta.edu.