Ultrasound assessment of subcutaneous compressibility: a potential adjunctive diagnostic tool in eosinophilic fasciitis.

Background: Eosinophilic fasciitis (EF) is an autoimmune, fibrotic disorder described initially with scleroderma-like skin changes where deep soft tissue sampling that includes fascia is frequently felt to be necessary to confirm the diagnosis.

Objective: The objective of this study was to distinguish forearm involvement by EF from other fibrosing diseases and from control subjects with normal skin and fascia using B-mode ultrasound.

Methods: A cross-sectional study over a 4-year period in which clinically involved forearm skin of consecutive patients with EF (n = 12), diabetic cheiroarthropathy (n = 8), diffuse systemic sclerosis (n = 23), and control subjects (n = 8) was evaluated by 12-MHz, B-mode ultrasound for degree of subcutaneous tissue compressibility, and this finding was compared with the criterion standard of clinical diagnostic criteria for each disease process.

Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.

Runx1 is a key hematopoietic transcription factor required for definitive hematopoiesis and is a frequent target of leukemia-related chromosomal translocations. The resulting fusion proteins, while retaining DNA binding activity, display loss of subnuclear targeting and associated transactivation functions encoded by the C-terminus of the protein. To define the precise contribution of the Runx1 C-terminus in development and leukemia, we created a knock-in mouse with a C-terminal truncation by introducing a single nucleic acid substitution in the native Runx1 locus.

Subnuclear targeting of Runx1 is required for synergistic activation of the myeloid specific M-CSF receptor promoter by PU.1.

Many types of acute myelogenous leukemia involve chromosomal translocations that target the C-terminus of Runx1/AML1 transcription factor, a master regulator of hematopoiesis. The C-terminus of Runx1/AML1 that includes the nuclear matrix targeting signal (NMTS) is essential for embryonic development, hematopoiesis, and target gene regulation. During the onset and normal progression of hematopoiesis, several lineage-specific factors such as C/EBPalpha and PU.

Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes.

Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage.

Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid differentiation, and effects a transformation-like phenotype.

The multifunctional C terminus of the hematopoietic AML1 transcription factor interacts with coregulatory proteins, supports the convergence and integration of physiological signals, and contains the nuclear matrix targeting signal, the protein motif that is necessary and sufficient to target AML1 to subnuclear sites. The (8;21) chromosomal translocation, which replaces the C terminus of AML1 with the ETO protein, modifies subnuclear targeting of AML1 in acute myeloid leukemia (AML) and results in defective myelopoiesis. We therefore addressed the relevance of AML1 subnuclear targeting and associated functions that reside in the C terminus to myeloid differentiation.

Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts.

The Runx2 (CBFA1/AML3/PEBP2alphaA) transcription factor promotes lineage commitment and differentiation by activating bone phenotypic genes in postproliferative osteoblasts. However, the presence of Runx2 in actively dividing osteoprogenitor cells suggests that the protein may also participate in control of osteoblast growth. Here, we show that Runx2 is stringently regulated with respect to cell cycle entry and exit in osteoblasts.