Ruth Curtis

Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the beta-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of beta-cells to insulin resistance.

Using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics, trends in female breast cancer rates were examined for the time period 1973-1989 for the age group 20-39 and contrasted with those for older ages. Only about 7% of breast cancers occur by the age of 40; the risk of developing breast cancer prior to the age of 40 is less than 1%. The incidence trends for women in the 20-39 age group have been essentially stable, whereas for women 40 and older the rates increased steeply during the 1980s (at a faster rate than anticipated based on historical trends) and then leveled off beginning in 1987. Breast cancer mortality has been much more stable over time than incidence. Up to age 40, blacks have a higher incidence than whites. Over age 40, white rates exceed those for blacks, and the absolute and relative differences in incidence increase with advancing age. For whites, 5-year relative survival rates improved with advancing age up to age 50. Blacks under the age of 30 had survival rates similar to whites, whereas, in the older age groups, whites had somewhat better survival rates overall and by stage. The occurrence of second cancers was also analyzed in women with a first invasive breast cancer. Cancers found to occur at higher than expected rates included leukemia and cancers of the breast, ovary, and lung.

This article reports on a study of the needs of families coping with life-threatening allergies in a child. Due to the scarcity of publications on the psychosocial dimensions of anaphylaxis, the authors draw on selected literature on family coping with chronic illness, asthma, and allergy to provide a conceptual context for the research and discussion of findings. Using qualitative methodology, parents from 17 families were interviewed about their experiences adjusting to a diagnosis of anaphylaxis in a child. From participants' responses about the nature and sources of information and support, parenting dilemmas, family activities, anxieties, challenges, and coping strategies, the authors identify patterns in the adaptive processes related to predictable developmental and episodic events that increase anxiety and support needs. Social work clinicians and other family-serving professionals can help families maintain an optimal balance between protective and debilitating anxiety. Potential interventions in community and health settings are suggested.

ABSTRACT Nonalcoholic steatohepatitis (NASH) is a common feature of the metabolic syndrome and toxic reactions to pharmacological drugs. Tamoxifen, (TMX) a widely used anti‐breast cancer drug, can induce NASH and changes in plasma cholesterol levels through mechanisms that are unclear. We studied primary actions of TMX using a short‐term treatment (5 days) that induces microvesicular hepatic steatosis and marked hypercholesterolemia in male rats. Using a combined approach of gene expression profiling and NMR‐based metabolite analysis, we found that TMX‐treated livers have increased saturated fatty acid content despite changes in gene expression, indicating decreased de novo lipogenesis and increased fatty acid oxidation. Our results show that TMX predominantly down‐regulates FAS expression and activity as indicated by the accumulation of malonyl‐CoA, a known inhibitor of mitochondrial β‐oxidation. In the face of a continued supply of exogenous free fatty acids, the blockade of fatty acid oxidation produced by elevated malonyl‐CoA is likely to be the major factor leading to steatosis. Use of a combination of metabolomic and transcriptomic analysis has allowed us to identify mechanisms underlying important metabolic side effects of a widely prescribed drug. Given the broader importance of hepatic steatosis, the novel molecular mechanism revealed in this study should be examined in other forms of steatosis and nonalcoholic steatohepatitis. Lelliott C. J., López M., Curtis R. K., Parker N., Laudes M., Yeo G., Jimenez‐Linan M., Grosse J., Saha A. K., Wiggins D., Hauton D., Brand M. D. O'Rahilly S., Griffin J. L., Gibbons G. F., Vidal‐Puig A. Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis. FASEB J. 19, 1–12 (2005)