Bcl-2 Inhibits the Innate Immune Response during Early Pathogenesis of Murine Congenital Muscular Dystrophy

Laminin α2 (LAMA2)-deficient congenital muscular dystrophy is a severe, early-onset disease caused by abnormal levels of laminin 211 in the basal lamina leading to muscle weakness, transient inflammation, muscle degeneration and impaired mobility. In a Lama2-deficient mouse model for this disease, animal survival is improved by muscle-specific expression of the apoptosis inhibitor Bcl-2, conferred by a MyoD-hBcl-2 transgene. Here we investigated early disease stages in this model to determine initial pathological events and effects of Bcl-2 on their progression. Using quantitative immunohistological and mRNA analyses we show that inflammation occurs very early in Lama2-deficient muscle, some aspects of which are reduced or delayed by the MyoD-hBcl-2 transgene. mRNAs for innate immune response regulators, including multiple Toll-like receptors (TLRs) and the inflammasome component NLRP3, are elevated in diseased muscle compared with age-matched controls expressing Lama2. MyoD-hBcl-2 inhibits induction of TLR4, TLR6, TLR7, TLR8 and TLR9 in Lama2-deficient muscle compared with non-transgenic controls, and leads to reduced infiltration of eosinophils, which are key death effector cells. This congenital disease model provides a new paradigm for investigating cell death mechanisms during early stages of pathogenesis, demonstrating that interactions exist between Bcl-2, a multifunctional regulator of cell survival, and the innate immune response

Skin grafting in a 3 year old Quarter Horse

The selected case involved a 3 year old Quarter Horse gelding that originally injured his right hind limb on high tensile wire fencing in April of 2010. The wound was small, approximately 4-5 cm, and was healing well. The same area was re-injured at the beginning of June. This time, the wound was much larger and encompassed the majority of the dorsal aspect of the metatarsus. Initially, the client’s regular veterinarian was handling the wound, but due to the severity of the injury, decided to refer the case to Cornell for further treatment. On presentation, the wound on the right hind fetlock was approximately 20cm long by 12cm wide distally, tapering to 3cm wide proximally. The granulation tissue was pale pink, glistening, and slightly raised above the edges of the skin. Due to the extensive size and location of the wound, a skin graft was chosen as the optimal treatment. Exuberant granulation tissue was resected and the area was bandaged. Two days later, the horse was taken to standing surgery for pinch grafting. 4-5 mm partial thickness pinch grafts were taken from the left side of the neck using a needle and #10 scalpel blade. Stab incisions were made 1cm apart into the granulation tissue bed on the right metatarsus using a #15 scalpel blade. The grafts were inserted using ophthalmic forceps. A sterile bandage was applied to the area and kept in place for 48 hours before changing to ensure the grafts stayed in place. After that, the bandage was changed every 3-4 days until recheck 4 to 6 weeks later. A silicone dressing was used after the first week to prevent the formation of excess granulation tissue at the graft site. Oral trimethoprim sulfa antibiotic was given BID for 7 days. The horse was confined to strict stall rest for the first 10-14 days then was hand walked for 4 weeks before turning out