Opposing Actions of Developmental Trichloroethylene and High-Fat Diet Coexposure on Markers of Lipogenesis and Inflammation in Autoimmune-Prone Mice.

Trichloroethylene (TCE) is a widespread environmental pollutant associated with immunotoxicity and autoimmune disease. Previous studies showed that mice exposed from gestation through early life demonstrated CD4+ T cell alterations and autoimmune hepatitis. Determining the role of one environmental risk factor for any disease is complicated by the presence of other stressors. Based on its known effects, we hypothesized that developmental overnutrition in the form of a moderately high-fat diet (HFD) consisting of 40% kcal fat would exacerbate the immunotoxicity and autoimmune-promoting effects of low-level (<10 µg/kg/day) TCE in autoimmune-prone MRL+/+ mice over either stressor alone. When female offspring were evaluated at 27 weeks of age we found that a continuous exposure beginning at 4 weeks preconception in the dams until 10 weeks of age in offspring that TCE and HFD promoted unique effects that were often antagonistic. For a number of adiposity endpoints, TCE significantly reversed the expected effects of HFD on expression of genes involved in fatty acid synthesis/insulin resistance, as well as mean pathology scores of steatosis. Although none of the animals developed pathological signs of autoimmune hepatitis, the mice generated unique patterns of antiliver antibodies detected by western blotting attributable to TCE exposure. A majority of cytokines in liver, gut, and splenic CD4+ T cells were significantly altered by TCE, but not HFD. Levels of bacterial populations in the intestinal ileum were also altered by TCE exposure rather than HFD. Thus, in contrast to our expectations this coexposure did not promote synergistic effects.

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series.

Bilateral multifocal upper extremity atypical granular cell tumors presenting as long-standing right wrist and left hand masses in a 15-year-old African-American female.

Granular cell tumor (GrCT) is a benign nerve sheath tumor. Atypical and malignant variants of GrCT are rare but have been well described. We report a case of multifocal symmetric atypical GrCT in the bilateral hand/wrists of a 15-year-old African-American female. The initial clinical impression for both masses was favored to be ganglion cysts. Ultrasound findings of both masses revealed hypoechoic soft tissue lesions with some internal echogenicity favoring complex cysts. On excision, both masses were histologically circumscribed, lobulated and attached to tendon. Large epithelioid cells with abundant granular eosinophilic cytoplasm arranged in syncytial cords and trabeculae percolated through collagen. Many cells had pleomorphism and/or prominent nucleoli. Mitotic figures, spindling, high nuclear-to-cytoplasmic ratio and necrosis were absent. Both masses showed diffuse S100 protein but negative desmin and pancytokeratin expression. Ki-67 index was 1% to 2%. p53 was positive in 5% to 10% of nuclei. Both masses met criteria for atypical (but not malignant) GrCT. Our case shows that atypical GrCT may be not only multifocal but also symmetric. We speculate that migration of defective neural crest stem cells along both upper limb buds during embryogenesis may have allowed these essentially identical tumors to arise in similar locations bilaterally simultaneously.

The minimal genome: a metabolic and environmental comparison.

The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered. This review analyzes the organisms Mycoplasma pneumoniae, Pelagibacter ubique, Vesicomyosocius okutanii and Prochlorococcus marinus as models of heterotrophic symbiont, heterotrophic free-living, autotrophic symbiont and autotrophic free-living organisms respectively and compares them to the current minimal cell model in order to determine which most closely resembles a true minimal genome. M. pneumoniae possesses a genome of 816 394 base pairs (bp) with 688 open reading frames (ORF) and a severely limited metabolism. Pelagibacter ubique possesses a 1 308 000 bp genome with 1354 ORF and has a fully functional metabolism but requires a reduced form of sulphur. Vesicomyosocius okutanii possesses a 1 020 000 bp genome with 975 ORF and is deficient in the production of threonine, isoleucine and ubiquinone. Prochlorococcus marinus possesses a 1 751 080 bp genome with 1884 ORF and has a complete metabolism with no deficiencies. The current minimal cell model requires a genome to be of limited size, culturalble and having minimal media requirements as such it is the conclusion of this review that P. marinus best fits this model. Further, future research should concentrate on genome reduction experiments using P. marinus and the search for additional minimal genomes should concentrate on autotrophic free-living organisms.