A physiological examination of mice harboring a null allele at the aryl hydrocarbon (Ah) locus revealed that the encoded aryl hydrocarbon receptor plays a role in the resolution of fetal vascular structures during development. Although the aryl hydrocarbon receptor is more commonly studied for its role in regulating xenobiotic metabolism and dioxin toxicity, a developmental role of this protein is supported by the observation that Ah null mice display smaller livers, reduced fecundity, and decreased body weights. Upon investigating the liver phenotype, we found that the decrease in liver size is directly related to a reduction in hepatocyte size. We also found that smaller hepatocyte size is the result of massive portosystemic shunting in null animals. Colloidal carbon uptake and microsphere perfusion studies indicated that 56% of portal blood flow bypasses the liver sinusoids. Latex corrosion casts and angiography demonstrated that shunting is consistent with the existence of a patent ductus venosus in adult animals. Importantly, fetal vascular structures were also observed at other sites. Intravital microscopy demonstrated an immature sinusoidal architecture in the liver and persistent hyaloid arteries in the eyes of adult Ah null mice, whereas corrosion casting experiments described aberrations in kidney vascular patterns.T he aryl hydrocarbon receptor (AHR) is a member of the per-arnt-sim (PAS) superfamily of proteins. The AHR regulates biological responses to a variety of environmental contaminants, such as the polycyclic aromatic hydrocarbons found in cigarette smoke, the polychlorinated dioxins that contaminate industrial chemicals, and the wartime defoliant Agent Orange (1-5). These chemical ligands bind to the AHR, leading to receptor dimerization with another PAS protein known as the aryl hydrocarbon nuclear translocator (ARNT). This heterocomplex interacts with genomic enhancer elements upstream of a battery of target genes that encode xenobiotic metabolizing enzymes (1, 6, 7). The observation that the up-regulated enzymes often have metabolic activity toward AHR agonists has led to the idea that this pathway represents an adaptive metabolic response that protects an organism from exposure to certain classes of toxic environmental contaminants. Although this adaptive role has considerable experimental support, this pathway is not always protective. Exposure to high-affinity AHR agonists, like the chlorinated dioxins, can result in cancer (8), immunosuppression (9), liver damage (10), and birth defects (11). The mechanisms underlying these toxic effects are unknown but appear to be AHR mediated.Because of its role in mediating responses to environmental contaminants, the biology of the AHR has been extensively characterized from a toxicological viewpoint. However, several observations suggest an additional role for the AHR in vertebrate development. First, a phylogenetic survey indicates that the AHR arose over 450 million years ago, with functional orthologs found in species that have evolved in vario...

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is an uncommon tumor of the skin. Clinically, it often masquerades as a benign, indolent tumor on the trunk and extremities. Microscopically, it extends far beyond assessed clinical margins, spreading locally in the dermis, subcutaneous tissue, and muscle. The local recurrence rate in patients with DFSP who undergo wide local excision ranges from 0% to 21%. Recent preliminary reports indicate more consistently favorable cure rates with Mohs micrographic surgery (MMS). However, to date only a few scattered reports have documented long‐term 5‐year follow‐up. The authors present data on 29 patients with DFSP who underwent MMS. In addition, they reviewed the medical literature to summarize the accumulated experience of MMS treatment in the management of DFSP. METHODS The authors conducted a retrospective review of a series of 40 consecutive patients with DFSP who underwent MMS over the last 20 years. Of these, there were 29 patients with > 5 years of follow‐up who formed the basis of the current review. The literature also was searched for patients with DFSP who underwent MMS with > 5 years of follow‐up RESULTS At the University of Wisconsin Mohs Surgery Clinic, 29 patients with > 5 years of follow‐up were treated. There were 16 women and 13 men. Eight patients developed recurrent disease after previous non‐Mohs treatment. Site distribution was 45% head and neck and 55% trunk and extremities. In the current series, there were no local recurrences, with a local 5‐year cure rate of 100%. In the literature review, which included the current series, there were 136 patients with DFSP who underwent Mohs surgery with > 5 years of follow‐up. Nine patients in the current series developed local recurrences, including five patients who underwent a second Mohs procedure. The local cure rates after the first and second Mohs surgeries were 93.4% and 98.5%, respectively. The rate (percent) and time to local recurrence was 50% at 3 years and 75% at 5 years. However, 25% of local recurrences appeared late, after the usual 5‐year recommendation. CONCLUSIONS In a series of 29 patients with of DFSP and in an accompanying update of the medical literature, 136 patients with DFSP underwent MMS with > 5 years of follow‐up. There were no regional and/or distant metastases. However, late recurrences beyond the usual recommended 5‐year follow‐up may occur. Therefore, all patients with DFSP, especially those with recurrent tumors, should be followed for an extended period. The accumulated data continue to confirm that, when DFSP is discovered early and is accessible readily to excision by MMS, a favorable outcome can be expected with minimal trauma or sacrifice of adjacent normal structures and with a low recurrence rate. Cancer 2004. © 2004 American Cancer Society.

We update the medical literature with 13 MAC cases treated by MMS. To our knowledge there have been 148 cases of MAC reported in the world literature. Including our series, there have been 73 cases of MAC treated with MMS. There were only four treatment failures. Regional and/or distant metastasis from MAC is rare, with only one reported death. Following MMS, the 2-year success rate was 89.7% (35 of 39). The accumulated data continue to confirm that when MAC is discovered early and is readily accessible to excision by MMS and other subspecialty support, a favorable outcome can be expected.

Summary Chronic wounds remain a major challenge in modern medicine and represent a significant burden, affecting not only physical and mental health, but also productivity, health care expenditure, and long-term morbidity. Even under optimal conditions, the healing process leads to fibrosis or scar. One promising solution, cell therapy, involves the transplantation of progenitor/stem cells to patients through local or systemic delivery, and offers a novel approach to many chronic diseases, including nonhealing wounds. Mesenchymal stem cells are multipotent, adult progenitor cells of great interest because of their unique immunologic properties and regenerative potential. A variety of preclinical and clinical studies have shown that mesenchymal stem cells may have a useful role in wound-healing and tissue-engineering strategies and both aesthetic and reconstructive surgery. Recent advances in stem cell immunobiology can offer insight into the multiple mechanisms through which mesenchymal stem cells could affect underlying pathophysiologic processes associated with nonhealing mesenchymal stem cells. Critical evaluation of the current literature is necessary for understanding how mesenchymal stem cells could potentially revolutionize our approach to skin and soft-tissue defects and designing clinical trials to address their role in wound repair and regeneration.