University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Abstract: background Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. methods Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. results Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 µ g per liter in 78 of 89 men (88 percent) and greater than 200 µ g per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 µ g per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. conclusions The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.

Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice.

Abstract: Interleukin 17 (IL-17) is a cytokine associated with inflammation, autoimmunity and defense against some bacteria. Here we show that IL-17 can promote autoimmune disease through a mechanism distinct from its proinflammatory effects. As compared with wild-type mice, autoimmune BXD2 mice express more IL-17 and show spontaneous development of germinal centers (GCs) before they increase production of pathogenic autoantibodies. We show that blocking IL-17 signaling disrupts CD4+ T cell and B cell interactions required for the formation of GCs and that mice lacking the IL-17 receptor have reduced GC B cell development and humoral responses. Production of IL-17 correlates with upregulated expression of the genes Rgs13 and Rgs16, which encode regulators of G-protein signaling, and results in suppression of the B cell chemotactic response to the chemokine CXCL12. These findings suggest a mechanism by which IL-17 drives autoimmune responses by promoting the formation of spontaneous GCs.

Micafungin versus Fluconazole for Prophylaxis against Invasive Fungal Infections during Neutropenia in Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract: 5 for the National Institute of Allergy and Infectious Diseases Mycoses Study Group a We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing !50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing !50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm (difference, 6.5%); 95% confidence interval, 0.9%-12%; ). This randomized trial demonstrates the efficacy of an P p .03

The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development

Abstract: Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia-inducible factor alpha (HIF alpha) pathway. Here we provide evidence that HIF alpha promotes angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice overexpressing HIF alpha in osteoblasts through selective deletion of the von Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones. By contrast, mice lacking Hif1a in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly thinner and less vascularized than those of controls. Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic metatarsals in vitro but had little effect on osteoblast function in the absence of blood vessels. Mice lacking both Vhl and Hif1a had a bone phenotype intermediate between those of the single mutants, suggesting overlapping functions of HIFs in bone. These studies suggest that activation of the HIF alpha pathway in developing bone increases bone modeling events through cell-nonautonomous mechanisms to coordinate the timing, direction, and degree of new blood vessel formation in bone.