Subject(s)
Leiomyosarcoma/secondary , Retroperitoneal Neoplasms/pathology , Stomach Neoplasms/secondary , Adult , Female , Humans , Leiomyosarcoma/diagnostic imaging , Polyps/diagnostic imaging , Retroperitoneal Neoplasms/diagnostic imaging , Stomach Neoplasms/diagnostic imaging , Tomography, X-Ray ComputedSubject(s)
Alcoholism/complications , Colon, Sigmoid , Foreign Bodies/complications , Gastrointestinal Hemorrhage/etiology , Colonoscopy , Eating , Humans , Male , Middle AgedSubject(s)
Gastritis , Hyperkalemia/drug therapy , Polystyrenes , Sorbitol , Stomach , Acute Kidney Injury/complications , Aged , Cathartics/administration & dosage , Cathartics/adverse effects , Chelating Agents/administration & dosage , Chelating Agents/adverse effects , Gastritis/chemically induced , Gastritis/diagnosis , Gastroscopy/methods , Humans , Hyperkalemia/etiology , Ischemia/chemically induced , Male , Necrosis/chemically induced , Polystyrenes/administration & dosage , Polystyrenes/adverse effects , Sorbitol/administration & dosage , Sorbitol/adverse effects , Stomach/blood supply , Stomach/diagnostic imaging , Stomach/pathology , Tomography, X-Ray Computed/methodsABSTRACT
We present a 24-year-old combat veteran who underwent extensive work-up for elevated aminotransferases, including liver biopsy, with no underlying pathology identified. Subsequent investigations showed elevated creatinine kinase and aldolase. The patient was later diagnosed with biopsy-proven dysferlin-deficient muscular dystrophy. Persistent transaminase elevation despite negative liver work-up should prompt clinicians to consider extrahepatic sources of enzyme elevation. Promptly correlating aminotransferase elevation with musculoskeletal pathology may present an opportunity for clinicians to detect myopathies such as muscular dystrophy in their preclinical stages.
Subject(s)
Esophagus/blood supply , Gastrointestinal Neoplasms/complications , Nevus, Blue/complications , Skin Neoplasms/complications , Vascular Diseases/etiology , Esophagus/pathology , Gastrointestinal Neoplasms/pathology , Humans , Male , Middle Aged , Nevus, Blue/pathology , Skin Neoplasms/pathology , Vascular Diseases/pathologySubject(s)
Abdominal Abscess/complications , Abdominal Abscess/diagnosis , Drainage , Endoscopy, Digestive System , Gastric Outlet Obstruction/etiology , Abdominal Abscess/pathology , Abdominal Abscess/surgery , Adult , Female , Gastric Outlet Obstruction/surgery , Humans , Peritoneal Cavity , Treatment OutcomeSubject(s)
Abdominal Pain , Dentures , Foreign Bodies , Ileocecal Valve/pathology , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Abdominal Pain/surgery , Aged , Colonoscopy/methods , Foreign Bodies/complications , Foreign Bodies/diagnosis , Foreign Bodies/physiopathology , Foreign Bodies/surgery , Humans , Male , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Development of pretransplantation islet culture strategies that preserve or enhance ß-cell viability would eliminate the requirement for the large numbers of islets needed to restore insulin independence in type 1 diabetes patients. We investigated whether glial cell line-derived neurotrophic factor (GDNF) could improve human islet survival and posttransplantation function in diabetic mice. METHODS: Human islets were cultured in medium supplemented with or without GDNF (100 ng/mL) and in vitro islet survival and function assessed by analyzing ß-cell apoptosis and glucose stimulated insulin release. In vivo effects of GDNF were assessed in streptozotocin-induced diabetic nude mice transplanted under the kidney capsule with 2000 islet equivalents of human islets precultured in medium supplemented with or without GDNF. RESULTS: In vitro, human islets cultured for 2 to 10 days in medium supplemented with GDNF showed lower ß-cell death, increased Akt phosphorylation, and higher glucose-induced insulin secretion than islets cultured in vehicle. Human islets precultured in medium supplemented with GDNF restored more diabetic mice to normoglycemia and for a longer period after transplantation than islets cultured in vehicle. CONCLUSIONS: Our study shows that GDNF has beneficial effects on human islet survival and could be used to improve islet posttransplantation survival.
Subject(s)
Diabetes Mellitus, Experimental/surgery , Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Graft Survival/drug effects , Insulin-Secreting Cells/drug effects , Islets of Langerhans Transplantation/methods , Islets of Langerhans/drug effects , Animals , Apoptosis/drug effects , Cells, Cultured , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Disease Models, Animal , Glucose/pharmacology , Humans , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Mice , Mice, Nude , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Streptozocin/adverse effects , Transplantation, HeterologousABSTRACT
Glial cell line-derived neurotrophic factor (GDNF) is a factor produced by glial cells that is required for the development of the enteric nervous system. In transgenic mice that overexpress GDNF in the pancreas, GDNF has been shown to enhance beta-cell mass and improve glucose control, but the transcriptional and cellular processes involved are not known. In this study we examined the influence of GDNF on the expression of neurogenin3 (Ngn3) and other transcription factors implicated in early beta-cell development, as well as on beta-cell proliferation during embryonic and early postnatal mouse pancreas development. Embryonic day 15.5 (E15.5) mouse pancreatic tissue when exposed to GDNF for 24 h showed higher Ngn3, pancreatic and duodenal homeobox gene 1 (Pdx1), neuroD1/beta(2), paired homeobox gene 4 (Pax4), and insulin mRNA expression than tissue exposed to vehicle only. Transgenic expression of GDNF in mouse pancreata was associated with increased numbers of Ngn3-expressing pancreatic cells and higher beta-cell mass at embryonic day 18 (E18), as well as higher beta-cell proliferation and Pdx1 expression in beta-cells at E18 and postnatal day 1. In the HIT-T15 beta-cell line, GDNF enhanced the expression of Pax6. This response was, however, blocked in the presence of Pdx1 small interfering RNA (siRNA). Chromatin immunoprecipitation studies using the HIT-T15 beta-cell line demonstrated that GDNF can influence Pdx1 gene expression by enhancing the binding of Sox9 and neuroD1/beta(2) to the Pdx1 promoter. Our data provide evidence of a mechanism by which GDNF influences beta-cell development. GDNF could be a potential therapeutic target for the treatment and prevention of diabetes.