Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can occur secondary to various infectious, malignant, and autoimmune triggers in patients without a known genetic predisposition. Clinical hallmarks are prolonged fever, cytopenias, hepatosplenomegaly, and neurological symptoms, but atypical variants presenting with signs of chronic immunodeficiency are increasingly recognized. Impaired secretion of perforin is a key feature in several genetic forms of the disease, but not required for disease pathogenesis. Despite progress in diagnostics and therapy, mortality of patients with severe HLH is still above 40%. Reference treatment is an etoposide-based protocol, but new approaches are currently explored. Key for a favorable prognosis is the rapid identification of an underlying genetic cause, which has been facilitated by recent immunological and genetic advances. In patients with predisposing genetic disease, hematopoietic stem cell transplantation is performed increasingly with reduced intensity conditioning regimes. Current research aims at a better understanding of disease pathogenesis and evaluation of more targeted approaches to therapy, including anti-cytokine antibodies and gene therapy.     

Methods of identifying and inseminating nonpregnant beef females after synchronization of second estrus with norgestomet implants

Beef females (547) were included in three experiments to evaluate methods of identifying and inseminating nonpregnant beef females after synchronization of second estrus with norgestomet implants. In the first experiment, heifers not pregnant to the first insemination were identified for insemination via estrus (inseminated via the a.m./p.m. rule or 48 h after implant removal). In the second experiment, females not pregnant to the first insemination were identified for insemination via estrus (inseminated via the a.m./p.m. rule) or progesterone concentrations < 1.5 ng/mL at implant removal (inseminated 48 h after implant removal). In the third experiment, heifers not pregnant to the first insemination were identified for insemination via progesterone concentrations (as in experiment 2) or anterior vagina electrical resistance values < 81 ohm resistance 48 h after implant removal (inseminated after resistance measured). All methods of identifying and inseminating nonpregnant females were equally effective (P > 0.10) and did not effect (P > 0.10) calving rates from the first and second AI.     

The ability of natural tolerance to be applied to allogeneic tissue: determinants and limits

Background  

Transplant rejection has been considered to occur primarily because donor antigens are not present during the development of the recipient's immune system to induce tolerance. Thus, transplantation prior to recipient immune system development (pre-immunocompetence transplants) should induce natural tolerance to the donor. Surprisingly, tolerance was often not the outcome in such 'natural tolerance models'. We explored the ability of natural tolerance to prevent immune responses to alloantigens, and the reasons for the disparate outcomes of pre-immunocompetence transplants.