Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R ‫؍‬ 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis. (Liver Transpl 2001;7:409-414.)

A novel estrogen receptor (ER)␣ coactivator complex, the MLL2 complex, which consists of MLL2, ASH2, RBQ3, and WDR5, was identified. ER␣ directly binds to the MLL2 complex through two LXXLL motifs in a region of MLL2 near the C terminus in a liganddependent manner. Disrupting the interaction between ER␣ and the MLL2 complex with small interfering RNAs specific against MLL2 or an MLL2 fragment representing the interacting region with ER␣ significantly inhibited the ER␣ transcription activity. The MLL2 complex was recruited on promoters of ER␣ target genes along with ER␣ upon estrogen stimulation. Inhibition of MLL2 expression decreased the estrogen-induced expression of ER␣ target genes cathepsin D and to a lesser extent pS2. In addition, MCF-7 cell growth was also inhibited by the depletion of MLL2. These results demonstrate that the ER␣ signaling pathway is critically dependent on its direct interaction with the MLL2 complex and suggest a central role for the MLL2 complex in the growth of ER␣-positive cancer cells.The biological effects of estrogen are mediated by estrogen receptors (ER) 2 in estrogen responsive tissues. There are two types of estrogen receptors, ER␣ and ER␤. The well studied ER␣ is involved in normal mammary gland development as well as breast cancer initiation and progress (1-4). ER␣ has two transcriptional activation domains, the N-terminal activation domain AF-1 and the C-terminal activation domain AF-2. Upon estrogen binding, ER␣ undergoes a conformational change and regulates the expression of its target genes (5, 6). ER␣, just as other nuclear receptors, requires coactivators and corepressors for its function. A large number of ER␣ coactivators, including the three members of the SRC-1 family (SRC-1, SRC-2/GRIP1/TIF2, and SRC-3/AIB1/ ACTR/pCID/RAC3/TRAM1) (7-9), CREB-binding protein (CBP/ p300), and TRAP220 (DRIP 205, PBP) (10, 11), have been identified to date. Most of the coactivators interact with the AF-2 domain of ER␣ in a ligand-dependent manner. Some of these cofactors are intrinsic enzymes with the activity of acetyltransferase or methyltransferase or are able to recruit such enzymes (12-14) that modify histone composition of chromatin to make transcription factors accessible to specific regions of the genome. The varying patterns of histone modification are now referred to as a histone code and are proposed to be epigenetic markers for determining gene activation status (15). Some nuclear receptor coactivators (corepressors) are presented as multiprotein complexes, and these steady-state protein complexes probably act as functional units of nuclear receptor coregulators (16). ER␣ coactivator TRAP220/PBP exists in the multiprotein TRAP complex, which has molecular mass of ϳ2 MD and is composed of more than 30 subunits (17). The TRAP complex facilitates ER␣ actions by synergizing basal transcription machineries. The ER␣ coactivator PRIP (TRBP, TRAP250, NRC, and AIB3) is also demonstrated to stay in a massive steady-state complex ASCOM (18), which consists of MLL4, PRIP (ASC2), MLL...

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