One of the major contributors to sickle cell disease (SCD) pathobiology is the hemolysis of sickle red blood cells (RBCs), which release free hemoglobin and platelet agonists including adenosine 5'-diphosphate (ADP) into the plasma. While platelet activation/aggregation may promote tissue ischemia and pulmonary hypertension in SCD, modulation of sickle platelet dysfunction remains poorly understood. Calpain-1, a ubiquitous calcium-activated cysteine protease expressed in hematopoietic cells, mediates aggregation of platelets in healthy mice.
View Article and Find Full Text PDFIndividuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the effects of a loss of autophagy in dendritic cells (DCs), as well as both B cells and DCs, in a TLR7-mediated model of autoimmunity, similar to systemic lupus erythematosus, where both cell types are critical for disease.
View Article and Find Full Text PDFSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, defined by loss of B cell self-tolerance that results in production of antinuclear antibodies (ANA) and chronic inflammation. While the initiating events in lupus development are not well defined, overexpression of the RNA-recognizing toll-like receptor (TLR)7 has been linked to SLE in humans and mice. We postulated that autophagy plays an essential role in TLR7 activation of B cells for the induction of SLE by delivering RNA ligands to the endosomes, where this innate immune receptor resides.
View Article and Find Full Text PDFTen veterinary pathologists at 1 veterinary institution independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors (MCTs). There was significant variation among pathologists in grading the MCTs (P < 0.001).
View Article and Find Full Text PDFJ Vet Diagn Invest
September 2004
A chordoma was removed from the tail base of a 6.5-year-old ferret (Mustela putorius furo). A nodule was observed in the area of tumor development when the ferret was purchased at 3 months of age.
View Article and Find Full Text PDFAm J Reprod Immunol
September 2003
Problem: Sprague-Dawley (SD) rats infected during pregnancy with Mycoplasma pulmonis display adverse pregnancy outcomes that are similar to those observed in women with chorioamnionitis and may provide a good model system for this disease. The placental lesions caused by this microorganism, however, have not been thoroughly characterized.
Method Of Study: Rats were infected with 10(7) colony-forming units (CFU) M.