ABSTRACT
In rats, maternal exposure to restraint stress during pregnancy can induce abnormalities in the cardiovascular and central nervous systems of the offspring. These effects are mediated by long-lasting hyperactivation of the hypothalamic-pituitary-adrenal axis. However, little is known about the potential effects of stress during pregnancy on metabolic systems. We examined the effect of restraint stress in pregnant mice on the liver function of their offspring. The offspring of stressed mothers showed significantly higher lipid accumulation in the liver after weaning than did the controls; this accumulation was associated with increased expression of lipid metabolism-related proteins such as alanine aminotransferase 2 diglyceride acyltransferase 1, peroxisome proliferator-activated receptor gamma and glucocorticoid receptor. Additionally, we observed increased levels of 11ß-hydroxysteroid dehydrogenase type 1, an intercellular mediator that converts glucocorticoid from the inactive to the active form, in the foetal and postnatal periods. These results indicate that restraint stress in pregnancy in mice induces metabolic abnormalities via 11ß-hydroxysteroid dehydrogenase type 1-related pathways in the foetal liver. It is therefore possible that exposure to stress in pregnant women may be a risk factor for metabolic syndromes (e.g. fatty liver) in children.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Lipid Metabolism , Liver/metabolism , Prenatal Exposure Delayed Effects , Stress, Psychological , Animals , Animals, Newborn , Female , Fetus/metabolism , Gene Expression , Mice, Inbred C57BL , PregnancyABSTRACT
Cancer vaccine that targets 'self'-antigens expressed at high levels in tumor cells is a potentially useful immunotherapy, but immunological tolerance often defeats this strategy. Here, we describe the use of a naked DNA vaccine encoding a self tumor antigen, tyrosinase-related protein 2, to whose N-terminus ubiquitin is fused in a 'nonremovable' fashion. Unlike conventional DNA vaccines, this vaccine broke the tolerance and induced protective immunity to melanoma in C57BL/6 mice, as evaluated by tumor growth, survival rate and lung metastasis. The protective immunity was cancelled in the proteasome activator PA28alpha/beta knockout mice. Moreover, this vaccination exhibited therapeutic effects on melanoma implanted before vaccination. Our findings provide evidence for the first time that naked DNA vaccines encoding a ubiquitin-fused self-antigen preferentially induce the main effector CD8+ T cells through efficient proteolysis mediated by the ubiquitin-proteasome pathway, and lead the way to strategies aimed at targeting tissue differentiation antigens expressed by tumors.
Subject(s)
Autoantigens/immunology , Cancer Vaccines/administration & dosage , Genetic Therapy/methods , Melanoma/therapy , Skin Neoplasms/therapy , Vaccines, DNA/administration & dosage , Animals , CD8-Positive T-Lymphocytes/immunology , Cytotoxicity Tests, Immunologic , Female , Interferon-gamma/analysis , Melanocytes/immunology , Melanoma/immunology , Mice , Mice, Inbred C57BL , Proteasome Endopeptidase Complex/metabolism , Signal Transduction , Skin Neoplasms/immunology , T-Lymphocyte Subsets/immunology , Ubiquitin/metabolismABSTRACT
We report a rare case of angiomyolipoma located in the subcutis on the nose. A 54-year-old female first noticed a small, asymptomatic mass on her nose in 1994 and underwent tumor excision in April 1999. Histopathological examination revealed a typical form of angiomyolipoma, showing a proliferation of mature adipocytes, smooth muscle fascicles, and small- to medium-sized blood vessels.
