Endometrial intraepithelial neoplasia.

CONTEXT: Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies. OBJECTIVE: To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty. DATA SOURCES: A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar. CONCLUSIONS: The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.

Selective deficiency of HIF-1alpha in myeloid cells influences secondary intention wound healing in mouse skin.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) influences myeloid cell function. In this study we examined the role of myeloid cell HIF-1alpha on wound healing in vivo using a cell-specific knockout (KO) mouse model. MATERIALS AND METHODS: HIF-1alpha KO mice and wild-type (WT) controls received 8 mm full thickness dorsal dermal wounds. Wound dimensions were measured until full closure. Tissue was obtained from 3-day-old wounds for (immuno-)histochemical analysis. Production of interleukin-1beta (IL-1beta) and nitric oxide (NO) in response to lipopolysaccharide (LPS) and/or desferrioxamine (DFX) was examined in vitro. RESULTS: Early wound closure occurred significantly faster in HIF-1alpha KO mice than in WT mice. Wounds of KO mice contained similar numbers of neutrophils and macrophages, but more activated keratinocytes, consistent with accelerated re-epithelialization. Interestingly, while LPS and LPS+DFX elicited a similar IL-1beta response in macrophages from the 2 mouse types, NO production was blunted in HIF-1alpha KO macrophages. CONCLUSION: Absence of HIF-1alpha in myeloid cells accelerates the early phase of secondary intention wound healing in vivo. This may be associated with a deficient ability of myeloid cells to initiate an appropriate NO production response. Pharmacologic modulators of HIF-1alpha should be explored in situations with abnormal wound healing.