Hypertension in response to placental ischemia during pregnancy: role of B lymphocytes.

Preeclampsia is associated with innate inflammatory response resulting in elevated tumor necrosis factor-α, agonistic autoantibodies to the angiotensin II type I receptor, and activation of endothelin 1 (ET-1). This study was designed to determine the role of B-cell depletion, resulting in agonistic autoantibodies to the angiotensin II type I receptor suppression to mediate hypertension via activation of ET-1 in the placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. To achieve this goal we examined the effect of RUPP on mean arterial pressure and ET-1 in the presence and absence of chronically infused rituximab (R; 250 mg/kg), a B-lymphocyte-suppressive agent used clinically to treat autoimmune diseases.

Role of angiotensin II type I receptor agonistic autoantibodies (AT1-AA) in preeclampsia.

Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are unclear. One important initiating event in preeclampsia is thought to be reduced placental perfusion leading to the production of a variety of factors that cause widespread dysfunction of the maternal vasculature. The major objective of this review is to discuss the potential role of a novel agonistic autoantibody to the angiotensin II type I receptor (AT1-AA) in mediating hypertension during pregnancy.

Absence of neurotoxicity with medicinal grade terbutaline in the rat model.

To evaluate neurological effects of terbutaline, rats were injected with saline, terbutaline (Sigma or American Pharmaceutical Partners (APP™)) at 0.5 mg/kg-d or 10 mg/kg-d between postnatal days (PND) 2-5 or 11-14. Brains collected 24 h after last injection were used to determine corpus-callosum thickness, Purkinje cell and neuronal number in the cerebellum.

Serine/threonine protein kinase SGK1 in glucocorticoid-dependent transdifferentiation of pancreatic acinar cells to hepatocytes.

Elevated glucocorticoid levels result in the transdifferentiation of pancreatic acinar cells into hepatocytes through a process that requires a transient repression of WNT signalling upstream of the induction of C/EBP-β. However, the mechanism by which glucocorticoid interacts with WNT signalling is unknown. A screen of microarray data showed that the serine/threonine protein kinase SGK1 (serum- and glucocorticoid-regulated kinase 1) was markedly induced in the model B-13 pancreatic rat acinar cell line after glucocorticoid treatment (which converts them into hepatocyte-like 'B-13/H' cells) and this was confirmed at the level of mRNA (notably an alternatively transcribed SGK1C form) and protein.

Comparison of health-related quality of life 5 years after SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial.

Purpose: The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session.

Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa.

Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas.

Oxidative stress studies of six TiO₂ and two CeO₂ nanomaterials: immuno-spin trapping results with DNA.

Six TiO₂ and two CeO₂ nanomaterials with dry sizes ranging from 6-410 nm were tested for their ability to cause DNA centered free radicals in vitro in the concentration range of 10-3,000 ug/ml. All eight of the nanomaterials significantly increased the adduction of the spin trap agent 5,5-dimethyl-1-pyroline N-oxide (DMPO) to DNA as measured by the experimental technique of immuno-spin trapping. The eight nanomaterials differed considerably in their potency, slope, and active concentration.

Mitochondrial amplification selectively increases doxorubicin sensitivity in breast cancer cells with acquired antiestrogen resistance.

The metabolic phenotype of cancer, characterized by uncoupled mitochondrial respiration and increased mitochondrial oxidative stress, is an attractive pharmacological target for sensitizing cancer cells to therapies that rely on oxidative stress for their tumor specific cytotoxicity. The identification of specific cancer sub-types for which metabolic priming of tumors prior to chemotherapy is beneficial is critical, particularly in heterogeneous diseases such as breast cancer. The effects of the thiazolidinedione drug troglitazone were examined in normal mammary epithelial cells and cancer cell lines representing three clinically relevant breast cancer phenotypes.

The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease.

Aim: The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease.

Methods: Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12.

P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease.

Objective: To determine the role of platelets in stimulating mouse and human neutrophil activation and pulmonary injury in sickle cell disease (SCD).

Methods And Results: Both platelet and neutrophil activation occur in SCD, but the interdependence of these events is unknown. Platelet activation and binding to leukocytes were measured in mice and patients with SCD and in controls.

Prenatal infection decreases calbindin, decreases Purkinje cell volume and density and produces long-term motor deficits in Sprague-Dawley rats.

The cerebellum is involved in the control of motor functions with Purkinje cells serving as the only output from the cerebellum. Purkinje cells are important targets for toxic substances and are vulnerable to prenatal insults. Intrauterine infection (IUI) has been shown to selectively target the developing cerebral white matter through lesioning, necrosis and inflammatory cytokine activation.

Intervening in infancy: implications for autism spectrum disorders.

There is a scarcity of empirically validated treatments for infants and toddlers under age 3 years with autism spectrum disorders (ASD), as well as a scarcity of empirical investigation into successful intervention characteristics for this population. Yet early screening efforts are focused on identifying autism risk in children under age 3 years. In order to build ASD interventions for infants and toddlers upon a foundation of evidence-based characteristics, the current paper presents the results of a systematic literature search and effect size analysis of efficacious interventions for infants and toddlers with other developmental disorders: those who were born prematurely, have developmental impairments, or are at high risk for developmental impairments due to the presence of a biological or familial condition associated with developmental impairments.

Neuroligin 1 is dynamically exchanged at postsynaptic sites.

Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signaling across the synapse, specify synaptic functions, and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks, and is thought to participate in cognitive diseases.

A nanoscale Ti∕GaAs metal-semiconductor hybrid sensor for room temperature light detection.

We report an individually addressable Ti∕GaAs metal-semiconductor hybrid optical nanosensor with positive photoresistance and a sensitivity that increases as the device dimensions shrink. The underlying physics relates to the crossover from ballistic to diffusive transport of the photoinduced carriers and the geometric enhancement of the effect associated with a Schottky-barrier-coupled parallel metal shunt layer. For a 250 nm device under 633 nm illumination we observe a specific detectivity of D(*)=5.

Generation and validation of canine single chain variable fragment phage display libraries.

Single chain variable region fragments (scFvs) are composed of an immunoglobulin (Ig) variable heavy (VH) and variable light (VL) chain joined by a flexible serine-glycine linker. They represent the smallest antibody fragments that maintain antigen specificity and they hold significant potential for therapeutic antigen targeting in vivo. Here we report on the design and validation of a series of degenerate primers that amplify the recombined variable regions of canine Ig heavy and light chain genes from lymphocyte cDNA.

Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease.

We showed previously that pulmonary function and arterial oxygen saturation in NY1DD mice with sickle cell disease (SCD) are improved by depletion of invariant natural killer T (iNKT) cells or blockade of their activation. Here we demonstrate that SCD causes a 9- and 6-fold induction of adenosine A(2A) receptor (A(2A)R) mRNA in mouse pulmonary iNKT and natural killer (NK) cells, respectively. Treating SCD mice with the A(2A)R agonist ATL146e produced a dose-dependent reversal of pulmonary dysfunction with maximal efficacy at 10 ng/kg/minute that peaked within 3 days and persisted throughout 7 days of continuous infusion.

Multimodality Imaging of a Saphenous Vein Graft Aneurysm.

The use of multimodality cardiac imaging including echocardiography, cardiac computed tomography and cardiac catheterization for the diagnosis of a saphenous vein graft aneurysm is described. (Echocardiography, ****;**:E1-E2).

Simultaneous dual frequency 1H and 19F open coil imaging of arthritic rabbit knee at 3T.

The combination of sensitive magnetic resonance techniques with a selective site-targeted nanoparticle contrast agent has a demonstrated utility for molecular imaging studies. By detecting a unique signature of the contrast agent, this approach can be employed to identify specific bio-molecular markers and observe cellular-level processes within a large and complex organism (e.g.

AR42J-B-13 cell: an expandable progenitor to generate an unlimited supply of functional hepatocytes.

Hepatocytes are the preparation of choice for Toxicological research in vitro. However, despite the fact that hepatocytes proliferate in vivo during liver regeneration, they are resistant to proliferation in vitro, do not tolerate sub-culture and tend to enter a de-differentiation program that results in a loss of hepatic function. These limitations have resulted in the search for expandable rodent and human cells capable of being directed to differentiate into functional hepatocytes.

Application of a real-time, calculable limiting form of the Renyi entropy for molecular imaging of tumors.

Previously, we reported new methods for ultrasound signal characterization using entropy, H(f); a generalized entropy, the Renyi entropy, I(f)(r); and a limiting form of Renyi entropy suitable for real-time calculation, I(f),(infinity). All of these quantities demonstrated significantly more sensitivity to subtle changes in scattering architecture than energy-based methods in certain settings. In this study, the real-time calculable limit of the Renyi entropy, I(f),(infinity), is applied for the imaging of angiogenic murine neovasculature in a breast cancer xenograft using a targeted contrast agent.

Disrupted pancreatic exocrine differentiation and malabsorption in response to chronic elevated systemic glucocorticoid.

Glucocorticoids are antiinflammatory therapeutics that have potent effects on cell differentiation. The aim of this study was to establish whether systemic glucocorticoid exposure significantly affects pancreatic differentiation in vivo because hepatocyte-like cells have been documented to occur in the diseased rodent pancreas. Expression of hepatic markers was examined in pancreata from mice genetically modified to secrete elevated circulating endogenous glucocorticoid [Tg(Crh)].

Fluidic measurement of electric field sensitivity of Ti-GaAs Schottky junction gated field effect biosensors.

We report the electric field and pH sensitivity of fluid gated metal-semiconductor hybrid (MSH) Schottky structures consisting of a Titanium layer on n-type GaAs. Compared to standard field-effect sensors, the MSH Schottky structures are 21 times more sensitive to electric field of -46.6 V/cm and show about six times larger resistance change as pH of the solution is decreased from 8.

Glucocorticoid-dependent transdifferentiation of pancreatic progenitor cells into hepatocytes is dependent on transient suppression of WNT signalling.

Developmentally, the pancreas and liver are closely related and pathological conditions - including elevated glucocorticoid levels - result in the appearance of hepatocytes in the pancreas. The role of the WNT signalling pathway in this process has been examined in the model transdifferentiating pancreatic acinar AR42J-B-13 (B-13) cell. Glucocorticoid treatment resulted in a transient loss of constitutive WNT3a expression, phosphorylation and depletion of beta-catenin, loss of beta-catenin nuclear localisation, and significant reductions in T-cell factor/lymphoid enhancer factor (Tcf/Lef) transcriptional activity before overt changes in phenotype into hepatocyte-like (B-13/H) cells.