ABSTRACT
Infection can induce hemophagocytic lymphohistiocytosis (HLH) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We herein report a 52-year-old man who had HLH and AAV simultaneously, possibly caused by Enterococcus faecalis infective endocarditis. The HLH diagnosis was based on the HLH-2004 criteria. AAV was diagnosed based on a positive result for proteinase-3 ANCA and necrotizing vasculitis of the small vessels on a skin biopsy. He eventually died and was sent for autopsy after combination treatment of valve replacement, antibiotics, and immunosuppressants, including corticosteroids. This case involved a challenging diagnosis and treatment of HLH with various complications in an adult.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Bacterial Infections , Endocarditis , Heart Diseases , Lymphohistiocytosis, Hemophagocytic , Male , Adult , Humans , Middle Aged , Enterococcus faecalis , Antibodies, Antineutrophil Cytoplasmic , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Bacterial Infections/complications , Heart Diseases/complications , Endocarditis/complicationsABSTRACT
Phthalate esters (PAEs) are man-made compounds that are used widely in industry, and the ubiquitous exposure of humans to PAEs has been reported. Although some PAEs have been suggested to function as xenoestrogens in in vitro systems, such as human estrogen receptors (ERs) expressed in Chinese hamster ovary (CHO)-K1 cells, few studies have attempted to elucidate whether PAEs affect human ERα/ERß-mediated signaling in human breast cancer cells (i.e., combination between human ERs and human cells). Thus, further experiments are needed in order to clarify the activities of PAEs. Among the 9 PAEs (carbon# in the side chains: 2-8) investigated, dibutyl phthalate (DBP), dipentyl phthalate (DPENP), and dicyclohexyl phthalate (DCHP) were found to exhibit strong anti-estrogenic activities in MCF-7 cells (ER-positive) in the presence of 1 nM 17ß-estradiol (E2). Since limited information is currently available on DPENP and DCHP, we herein focused on these two PAEs. Experiments using MDA-MB-231 cells (ER-negative) transfected with human ERα or ERß expression plasmids revealed that DCHP was a markedly stronger anti-estrogenic PAE than DPENP; DCHP inhibited ERα and ERß activities stimulated by 1 nM E2 with IC50 values of ~5 and 11.2 µM, respectively. Furthermore, DCHP abrogated diarylpropionitrile (DPN)-stimulated ERß activity with an IC50 value of 5.17 µM, which was approximately 2-fold stronger than that of DPENP (IC50 = 10 µM). The results of the present study suggest that PAEs (DCHP) function not only as an anti-estrogen for ERα, but also for ERß, at least in human breast cancer cell lines.