Re-epithelialization of skin wounds depends upon the migration of keratinocytes from the cut margins of the wound and is enhanced when human keratinocytes are covered with occlusive dressings that induce hypoxia. In this study, two independent migration assays were used to compare cellular motility on connective tissue components under normoxic or hypoxic conditions. Human keratinocytes apposed to collagens or fibronectin exhibited increased motility when subjected to hypoxic (0.2 or 2% oxygen) conditions compared with normoxic (9 or 20% oxygen) conditions. When compared with normoxic cells, hypoxic keratinocytes exhibited increased expression and redistribution of the lamellipodia-associated proteins (ezrin, radixin, and moesin). Furthermore, hypoxic keratinocytes demonstrated decreased secretion of laminin-5, a laminin isoform known to inhibit keratinocyte motility. Hypoxia did not alter the number of integrin receptors on the cell surface, but did induce enhanced secretion of the 92-kD type IV collagenase. These data demonstrate that hypoxia promotes human keratinocyte motility on connective tissue. Hypoxia-driven motility is associated with increased expression of lamellipodia proteins, increased expression of collagenase and decreased expression of laminin-5, the locomotion brake for keratinocytes. (
Human bullous pemphigoid (BP) is an immune-mediated blistering disease characterized by autoantibodies against BP antigens (230/180 kd), which are constitutive glycoproteins of hemidesmosomes found in basal keratinocytes. Blistering diseases similar to human BP have been reported in dogs. IgG deposits at the basement membrane zone (BMZ) are a common feature of canine BP. Although circulating anti-BMZ IgG autoantibodies have been demonstrated in some cases of canine BP, the specific skin protein targeted by these autoantibodies has not been identified. In this study, we characterized the antigenic target of the autoantibodies in the serum from a 3-year-old castrated male Pit Bull Terrier with BP. Direct immunofluorescence of the patient's skin demonstrated IgG deposits at the dermal-epidermal junction. Indirect immunofluorescence demonstrated autoantibodies in the patient's serum that stained the epidermal roof of salt-split canine skin and left the dermal floor unstained. These serum autoantibodies did not stain normal intact dog skin but labeled intact bovine tongue. Direct immunoelectron microscopy of the dog's skin revealed IgG deposits within the hemidesmosomes of the basal keratinocytes. Western immunoblotting experiments showed that canine keratinocytes express both the 230-kd and 180-kd bullous pemphigoid antigens, and the autoantibodies from the patient's serum recognized the 180-kd bullous pemphigoid antigen in proteins extracted from canine and human keratinocytes. Canine BP has many parallel features with human BP including similar immune deposition of IgG within hemidesmosomes and a hemidesmosome-associated 180-kd glycoprotein target for circulating autoantibodies.
DCP fixation is most likely the most stable form of fixation for comminuted interdental space fractures. However, for simple interdental space fractures, ISW fixation may provide adequate stability with minimal invasiveness and decreased expense. Tension-band wiring significantly enhances the strength of type II external skeletal fixators and should be used to augment mandibular fracture repairs.
A 27-month-old Rocky Mountain Horse was examined because of a fracture of the proximal portion of the ulna and luxation of the humeroradial joint (Monteggia fracture). Open reduction was performed, using a mechanical distractor, and the ulnar fracture was stabilized by application of a bone plate and screws. After surgery, the horse developed an infection of the surgical site, and bacterial culture of fluid from the surgical site yielded a pure growth of methicillin-resistant Staphylococcus epidermidis susceptible to oxytetracycline, erythromycin, rifampin, and vancomycin. Treatment with oxytetracycline did not result in a favorable clinical response. Therefore, the horse was treated systemically with vancomycin and rifampin, and vancomycin-impregnated polymethyl methacrylate beads were implanted at the surgical site. Six months after surgery, the horse was sound at a walk or trot, and bony union was evident on radiographs of the elbow joint.
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