Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Comparative analysis of mRNA and protein expression of Popdc1 (Bves) during early development in the chick embryo.

The isolation of the Popeye gene family was based on its preferential expression in striated muscle tissue. Recently, a monoclonal antibody against chick Popdc1 (also known as Bves) became available and was used in this study to comparatively analyze the expression pattern of Popdc1 at both the protein and mRNA level during early chick embryogenesis. Using whole-mount immunohistochemistry, expression in the heart was first observed at Hamburger and Hamilton (HH) stage 10 in the presumptive left ventricular segment. Cardiac expression was confined to differentiated cardiac myocytes, and undifferentiated myocytes at the anterior and posterior pole showed little expression. After looping, the outer curvature myocardium showed prominent Popdc1 staining, whereas the inner curvature was unlabeled. Despite previous reports, Popdc1 protein was not detectable at any time point in the proepicardium, epicardium, or the smooth muscle layer of the coronary vessels. Whole-mount in situ hybridization using a full-length Popdc1 probe detected novel expression domains, which have not been described previously. Popdc1 mRNA was found in Hensen's node at HH stage 4, and by HH stage 5+, expression became asymmetric. In addition, Popdc1 mRNA was found in pharyngeal endoderm and in the notochordal plate. Subsequently, beginning at HH stage 9, Popdc1 mRNA expression was found in the cardiac mesoderm and expression was maintained in the heart in a pattern very similar to the one observed by antibody staining.     

Phonological features of child African American English.

The production of phonological features of African American English (AAE) was examined for 64 typically developing African American children in the 2nd through the 5th grade. Students read aloud passages written in Standard American English. Sixty of the students read the passages using AAE, and 8 different phonological features were represented in their readings. Phonological features were more frequent than morphosyntactic features. The findings as a whole support use of the taxonomy developed for this investigation in characterizing the phonological features of child AAE.     

Conservation of the chromatophore pigment response

Toxicant sensing technology has evolved to include biological sensors, such as cell‐based biosensors, which rely on viable cells to convey a measurable physiological signal. Chromatophores are a class of pigment cells that have been investigated as cell‐based biosensors. We report the characterization of Oncorhynchus tshawytscha melanophores and describe the melanophore pigment response to neurotransmitters in terms of pigment area occupied. Compared with the previously described model, Betta splendens erythrophores, O. tshawytscha melanophores responded similarly, indicating that pigment responses are biologically conserved between these two species. Additionally, melanophores responded to mercuric chloride and sodium arsenite, similar to B. splendens erythrophores, suggesting that melanophores can be used as detectors for environmental toxicants. This report highlights the potential of O. tshawytscha melanophores to be used as cell‐based biosensors to address environmental toxicity, and warrants a continued investigation to strengthen this technology and its applications.     

The Hyperplantarflexion Ankle Fracture Variant

Various patterns of ankle fractures that are not accounted for by common classification systems have been the subject of case reports. The first difficulty with these variant patterns is recognizing all associated pathology, followed by the successful application of stable fixation. The purpose of this study was to describe the common morphologic features and ligamentous injuries of a unique variant fracture pattern, as well as the surgical treatment technique and the short-term functional and radiographic outcomes. Of 121 consecutive unstable ankle fractures over a 2-year period, 7 patients were found to have a similar constellation of injuries around the ankle. A vertical shear fracture of the posteromedial tibial rim was the main feature. Six of the 7 also had a fracture of the posterior malleolus. On magnetic resonance imaging, the deltoid and posterior tibiofibular ligaments were intact in all cases. Fractures were treated with open anatomic reduction of the posteromedial and posterior fragments with antiglide plate fixation. All fractures healed at 2 months without loss of reduction, fixation failure, or surgical complications. The average American Academy of Orthopaedic Surgeons lower extremity score was 79 at an average of 8 months' follow-up. The common radiographic and morphologic features associated with this posteromedial fracture indicate that it likely occurs through a common mechanism that involves hyperplantarflexion. The characteristics of this fracture pattern have not been fully described previously, but this ankle fracture variant may occur in up to 6% of cases. Unstable ankle fractures should be evaluated carefully for evidence of posteromedial involvement so appropriate treatment may proceed.     

Impaired motor imagery in patients with essential tremor: a case control study.

Motor imagery (MI), which refers to the process of mental representation of movements, has not been studied in patients with essential tremor (ET). We investigated the presence of impaired MI in ET patients compared with healthy controls. A group of drug-naive and nondemented ET patients and age-matched controls were studied using transcranial magnetic stimulation, while they were specifically instructed to try and imagine themselves performing two motor tasks. The various clinical and electrophysiological variables were evaluated and compared. Repeated measures ANOVA demonstrated a significant difference between ET patients and controls with respect to mean motor-evoked potential (MEP) amplitudes (F(1,38) = 31.92, P < 0.005) during MI. The process of MI effectively facilitated MEP amplitude in controls but not in ET patients, regardless of side of stimulation or motor tasks. We provide evidence to demonstrate impairment of MI in a group of ET patients compared with healthy controls. The basis for this novel finding is unclear, and further studies are warranted to determine whether it is related to cerebellar or motor cortical dysfunction.     

Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes.

Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor.