Deficient activation and resistance to activation-induced apoptosis of CD8+ T cells is associated with defective peripheral tolerance in nonobese diabetic mice.

Activation-induced cell death (AICD) is a mechanism of homeostasis that limits the clonal expansion of autoreactive T cells and regulates central and peripheral tolerance. In nonobese diabetic (NOD) mice, defects in central and peripheral tolerance are associated with a proliferative hyporesponsiveness of thymocytes and peripheral T cells elicited upon TCR activation. We investigated whether these defects in tolerance induction and hyporesponsiveness of NOD T cells manifest in an altered susceptibility to TCR-induced AICD.

SDF-1 enhances the expansion and maintenance of highly purified human hematopoietic progenitors.

The stromal-derived factor-1 (SDF-1) chemokine and its putative receptor, CXCR4, have been implicated in hematopoiesis. Here we aim to characterize the effects of cytokine-induced CXCR4 expression and SDF-1 treatment on primitive human umbilical cord blood (CB) cells in vitro. Highly purified CD34+CD38-Lin-CXCR4- blood cells were capable of forming CD34+CXCR4+ cells during short-term liquid culture, but maintained distinct erythroid and myeloid progenitor composition, similar to the parent population prior to culture.

A pulsating coronary vessel phantom for two- and three-dimensional intravascular ultrasound studies.

The evaluation of new techniques for 2-D and 3-D intravascular ultrasound (US) imaging (IVUS) often requires the use of a pulsating coronary phantom. This study describes the design, construction and evaluation of a phantom simulating the pulsation of a human coronary artery for IVUS studies. Polyvinyl alcohol (PVA) cryogel was used as a tissue mimic for the coronary vessel, which was incorporated in a custom-built assembly.

Functional regulation of choline acetyltransferase by phosphorylation.

Choline acetyltransferase (ChAT) catalyzes synthesis of acetylcholine (ACh) in cholinergic neurons. ACh synthesis is regulated by availability of precursors choline and acetyl coenzyme A or by activity of ChAT; ChAT regulates ACh synthesis under some conditions. Posttranslational phosphorylation is a common mechanism for regulating the function of proteins.

Serp-1, a viral anti-inflammatory serpin, regulates cellular serine proteinase and serpin responses to vascular injury.

Complex DNA viruses have tapped into cellular serpin responses that act as key regulatory steps in coagulation and inflammatory cascades. Serp-1 is one such viral serpin that effectively protects virus-infected tissues from host inflammatory responses. When given as purified protein, Serp-1 markedly inhibits vascular monocyte invasion and plaque growth in animal models.

MP3 compression of Doppler ultrasound signals.

The effect of lossy, MP3 compression on spectral parameters derived from Doppler ultrasound (US) signals was investigated. Compression was tested on signals acquired from two sources: 1. phase quadrature and 2.

Characterization of a pan-species reactive monoclonal antibody specific for a cell surface epitope which could serve as a marker for human monocytic and megakaryocytic differentiation.

A mouse IgG(1)-producing hybridoma, CSC-31, was isolated and characterized. The monoclonal antibody (MAb) was originally raised against monkey kidney cell-surface molecules. FACS analysis further showed that CSC-31 exhibited broad tissue and species reactivity.

Neutralizing intraspinal nerve growth factor with a trkA-IgG fusion protein blocks the development of autonomic dysreflexia in a clip-compression model of spinal cord injury.

Increased intraspinal nerve growth factor (NGF) after spinal cord injury (SCI) is detrimental to the autonomic nervous system. Autonomic dysreflexia is a debilitating condition characterized by episodic hypertension, intense headache, and sweating. Experimentally, it is associated with aberrant primary afferent sprouting in the dorsal horn that is nerve growth factor (NGF)-dependent.

Chronic pain after clip-compression injury of the rat spinal cord.

Chronic tactile allodynia and hyperalgesia are frequent complications of spinal cord injury (SCI) with poorly understood mechanisms. Possible causes are plastic changes in the central arbors of nociceptive and nonnociceptive primary sensory neurons and changes in descending modulatory serotonergic pathways. A clinically relevant clip-compression model of SCI in the rat was used to investigate putative mechanisms of chronic pain.

Comparison of core needle breast biopsy techniques: freehand versus three-dimensional US guidance.

Rationale And Objectives: No single method is generally accepted for evaluating the accuracy of breast biopsy techniques before their clinical implementation. The purpose of this study was to test a new process for evaluating biopsy techniques by using it in the evaluation of a prototype three-dimensional ultrasound (US)-guided biopsy device.

Materials And Methods: The biopsy accuracy of a new three-dimensional US-guided breast biopsy device was compared to that of the accepted clinical practice of biopsy by expert radiologists with two-dimensional freehand US guidance.

Stroke prevention in the elderly.

The incidence of stroke and risk factors peak in subjects > or = 75 years. Highest risk patients benefit most from effective therapy. For this reason, all strategies of proven value in stroke prevention must be assiduously applied.

Inhibition of the apical sodium-dependent bile acid transporter reduces LDL cholesterol and apoB by enhanced plasma clearance of LDL apoB.

Objective: Cloning of the ileal apical sodium-dependent bile acid transporter (ASBT) has identified a new pharmacological target for the modulation of plasma lipoproteins. The objective of this study was to determine whether a novel, specific, minimally absorbed ASBT inhibitor (SC-435) decreases LDL cholesterol through the alteration of plasma apoB kinetics.

Methods And Results: Miniature pigs were treated for 21 days with 10 mg/kg/day of SC-435 or placebo.

Adverse drug reactions to protease inhibitors.

Protease inhibitors are drugs that are commonly used in the therapy of people living with HIV infection. These drugs are commonly used in combination and act by inhibiting viral protease, blocking viral replication. Adverse drug reactions to protease inhibitors include gastrointestinal problems, rash and metabolic disturbances.

Theoretical and experimental quantification of carotid plaque volume measurements made by three-dimensional ultrasound using test phantoms.

An accurate technique that exhibits low variability has practical importance for the quantification of carotid plaque volume. Such a technique is necessary to monitor plaque progression or regression that may result in response to nonsurgical therapy. In this study, we investigate the accuracy and variability of plaque volume measurement by three-dimensional ultrasound using vascular plaque phantoms over a range of 68.

Emergence of muscle and neural hematopoiesis in humans.

During human development, hematopoiesis is thought to be compartmentalized to the fetal circulation, liver, and bone marrow. Here, we show that combinations of cytokines together with bone morphogenetic protein-4 and erythropoietin could induce multiple blood lineages from human skeletal muscle or neural tissue. Under defined serum-free conditions, the growth factors requirements, proliferation, and differentiation capacity of muscle and neural hematopoiesis were distinct to that derived from committed hematopoietic sites and were uniquely restricted to CD45(-)CD34(-) cells expressing the prominin AC133.

Myeloid dendritic cells in non-obese diabetic mice have elevated costimulatory and T helper-1-inducing abilities.

Type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse begins with activation of islet-reactive T helper-1 (Th1) cells by dendritic cells (DCs). Since multiple genetic loci contribute to T1D, we evaluated the hypothesis that NOD DCs possess inherent characteristics that contribute to the autoimmune phenotype. When compared to a representative Th1 (C57BL/6) and Th2 (BALB/C) control strain, in vitro generated NOD myeloid DCs matured normally.

The development and evaluation of a three-dimensional ultrasound-guided breast biopsy apparatus.

We have designed a prototype three-dimensional ultrasound guidance (3D USB) apparatus to improve the breast biopsy procedure. Features from stereotactic mammography and free-hand US-guided biopsy have been combined with 3D US imaging. This breast biopsy apparatus accurately guides a needle into position for the sampling of target tissue.

Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters.

The grapefruit flavonoid, naringenin, is hypocholesterolemic in vivo, and inhibits basal apolipoprotein B (apoB) secretion and the expression and activities of both ACAT and microsomal triglyceride transfer protein (MTP) in human hepatoma cells (HepG2). In this report, we examined the effects of naringenin on apoB kinetics in oleate-stimulated HepG2 cells and determined the contribution of microsomal lumen cholesteryl ester (CE) availability to apoB secretion. Pulse-chase studies of apoB secretion and intracellular degradation were analyzed by multicompartmental modeling.

High resolution fMRI of ocular dominance columns within the visual cortex of human amblyopes.

Non-human primate models suggest that amblyopia has a neural basis in the form of a massive reduction in binocular neurons, and in some cases, a shift in ocular dominance of neural activity toward the unaffected eye. To date, the resolution of neuroimaging has been insufficient to investigate the neural basis of ocular dominance in human amblyopia. We used high spatial resolution (0.

Expression analysis of a novel p75(NTR) signaling protein, which regulates cell cycle progression and apoptosis.

Neurotrophin receptor-interacting MAGE (NRAGE) is the most recently identified p75 neurotrophin receptor (p75(NTR)) intracellular binding protein. Previously, NRAGE over-expression was shown to mediate cell cycle arrest and facilitate nerve growth factor (NGF) dependent apoptosis of sympathetic neuroblasts in a p75(NTR) specific manner. Here we have examined the temporal and spatial expression patterns of NRAGE over the course of murine embryogenesis to determine whether NRAGE's expression is consistent with its proposed functions.

Material-specific analysis using coherent-scatter imaging.

Coherent-scatter computed tomography (CSCT) is a novel imaging method we are developing to produce cross-sectional images based on the low-angle (<10 degrees) scatter properties of tissue. At diagnostic energies, this scatter is primarily coherent with properties dependent upon the molecular structure of the scatterer. This facilitates the production of material-specific maps of each component in a conglomerate.