Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure.

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells' inflammatory phenotype may impact obesity and its complications.

Bilateral hand transplantation: Functional benefits assessment in five patients with a mean follow-up of 7.6 years (range 4-13 years).

Between January 2000 and July 2009, five adults who had suffered bilateral traumatic below-elbow amputations, received bilateral hand-forearm allografts performed by the Lyon team. We report the functional benefits achieved over a mean follow-up period of 7.6 years (range 4-13 years), up to December 31st, 2013. Clinical measurement is hampered by the lack of specific validated assessment tools, obliging us to use non-specific standardized evaluation means. Our assessment shows that the restoration of motion, strength, and sensibility are fair. Functional results (Carroll upper extremity function test, 400-point test, Activities of daily living) are good, as well as quality of life evaluation (RAND-36). Subjective and overall results explored with questionnaires - Disabilities of the Arm Shoulder and Hand (DASH), Hand Transplantation Score System (HTSS), are very good. Improvement was seen to continue during the first three years, and then tend to become stable. Continued efforts should be directed at designing comprehensive, condition-specific, reliable outcome measurement tools. Continuous monitoring and evaluation of patients is required to assess the long-term risk-benefit balance.

Accurate assessment of HER2 gene status for invasive component of breast cancer by combination of immunohistochemistry and chromogenic In Situ hybridization.

The specimens of ductal carcinoma in situ (DCIS) with early invasion, and specimens collected by core needle biopsy (CNB) tend to contain limited amount of invasive component, so it is imperative to explore a new technique which can assess HER2 gene status accurately for the limited invasive cancer component in these specimens. Dual staining technique of combining immunohistochemistry (IHC) for myoepithelial cells and single or dual probe chromogenic in situ hybridization (CISH) for HER2 gene was performed on routinely processed paraffin sections from 20 cases diagnosed as having DCIS with invasive cancer. Among them, 10 had fluorescence in situ hybridization (FISH)-confirmed amplification of HER2 and 10 had FISH-confirmed non-amplification of HER2. We successfully detected HER2 genetic signals and myoepithelial IHC markers (SMM-HC or CK5/6) simultaneously on a single section in all 20 specimens. Myoepithelial markers and HER2 signals detected by dual staining assay were consistent with those by individual technique performed alone. HER2 gene amplification results determined by dual staining assay were 100% consistent with those of FISH. Dual staining technique which allows simultaneous detection of myoepithelial marker protein and cancerous HER2 gene is feasible, and it has potential to be used in clinical practice for effective determination of HER2 amplification in limited invasive component.