Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.

ObjectiveTo analyze a series of patients treated for recurrent or chronic abdominal wall hernias and determine a treatment protocol for defect reconstruction. Summary Background DataComplex or recurrent abdominal wall defects may be the result of a failed prior attempt at closure, trauma, infection, radiation necrosis, or tumor resection. The use of prosthetic mesh as a fascial substitute or reinforcement has been widely reported. In wounds with unstable soft tissue coverage, however, the use of prosthetic mesh poses an increased risk for extrusion or infection, and vascularized autogenous tissue may be required to achieve herniorrhaphy and stable coverage. MethodsPatients undergoing abdominal wall reconstruction for 106 recurrent or complex defects (104 patients) were retrospectively analyzed. For each patient, hernia etiology, size and location, average time present, technique of reconstruction, and postoperative results, including recurrence and complication rates, were reviewed. Patients were divided into two groups based on defect components: Type I defects with intact or stable skin coverage over hernia defect, and Type II defects with unstable or absent skin coverage over hernia defect. The defects were also assigned to one of the following zones based on primary defect location to assist in the selection and evaluation of their treatment: Zone 1A, upper midline; Zone IB, lower midline; Zone 2, upper quadrant; Zone 3, lower quadrant. ResultsA majority of the defects (68%) were incisional hernias. Of 50 Type I defects, 10 (20%) were repaired directly, 28 (56%) were repaired with mesh only, and 12 (24%) required flap reconstruction. For the 56 Type II defects reconstructed, flaps were used in the majority of patients (n ϭ 48; 80%). The overall complication and recurrence rates for the series were 29% and 8%, respectively.

Secondary alveolar bone grafting of the cleft defect in our center was successful, based on radiographic outcome using cone beam computed tomography scans. Volume rendering using cone beam computed tomography and Amira software is a reproducible and practical method to assess the preoperative alveolar cleft volume and the adequacy of bone fill postoperatively.

Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms. The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance. Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi. Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.

Together our results suggest that restoring Hox A5 expression may provide a novel means to limit breast tumor growth or expansion of hemangiomas.