Comparative effects of halogenated inhaled anesthetics on voltage-gated Na+ channel function.

Background: Inhibition of voltage-gated Na channels (Na(v)) is implicated in the synaptic actions of volatile anesthetics. We studied the effects of the major halogenated inhaled anesthetics (halothane, isoflurane, sevoflurane, enflurane, and desflurane) on Na(v)1.4, a well-characterized pharmacological model for Na(v) effects.

Towards a curative therapy in type 1 diabetes: remission of autoimmunity, maintenance and augmentation of beta cell mass.

Recent clinical trials have shown that the loss of insulin production that characterizes progressive type 1 diabetes mellitus can be attenuated by treatment with non-FcR binding anti-CD3 monoclonal antibody (mAb). This approach is a first step towards the ultimate goals of treatment: to improve and maintain insulin production. However, additional interventions will be needed because, with time, there is progressive loss of insulin production after treatment with a single course of anti-CD3 mAb.

Rapid DNA amplification using a battery-powered thin-film resistive thermocycler.

A prototype handheld, compact, rapid thermocycler was developed for multiplex analysis of nucleic acids in an inexpensive, portable configuration. Instead of the commonly used Peltier heating/cooling element, electric thin-film resistive heater and a miniature fan enable rapid heating and cooling of glass capillaries leading to a simple, low-cost Thin-Film Resistive Thermocycler (TFRT). Computer-based pulse width modulation control yields heating rates of 6-7 K/s and cooling rates of 5 K/s.

A simple portable electroluminescence illumination-based CCD detector.

In this chapter we describe a simple and relatively inexpensive Electroluminescence (EL) illumination and charged-coupled device (CCD) camera (EL-CCD) based detector for monitoring fluorescence and colorimetric assays. The portable battery-operated fluorescence detector includes an EL panel for fluoro-genic excitation at 490 nm, a cooled CCD digital camera to monitor emission at 523 nm, filters and a close up lens. The detector system is controlled by a laptop computer for camera operation, image acquisition and analysis.

Human regulatory CD8 T cells.

Administration of a humanized monoclonal anti-CD3 antibody (mAb) to patients with type 1 diabetes (T1D) increases their C-peptide responses and the CD8/CD4 ratio. Incubation of human peripheral blood mononuclear cells (PBMC) with mAb in vitro has been shown to induce CD8(+) regulatory T cells (Tregs) capable of inhibiting proliferation of CD4(+) T cells. We hypothesized that CD8(+) Tregs function through secretion of cytokines.

Beta-cell mass and type 1 diabetes: going, going, gone?

Objective: Beta-cell regeneration is a fundamental but elusive goal for type 1 diabetes research. Our objective is to review newer human and animal studies of beta-cell destruction and regeneration and consider the implications for treatment of type 1 diabetes.

Research Design And Methods: Recent human and animal studies of beta-cell destruction and regeneration in type 1 diabetes are reviewed.

Promotion of beta-cell differentiation in pancreatic precursor cells by adult islet cells.

It is thought that differentiation of beta-cell precursors into mature cells is largely autonomous, but under certain conditions differentiation can be modified by external factors. The factors that modify beta-cell differentiation have not been identified. In this study, we tested whether adult islet cells can affect the differentiation process in mouse and human pancreatic anlage cells.

Generation and function of human regulatory CD8+ T cells induced by a humanized OKT3 monoclonal antibody hOKT3gamma1 (Ala-Ala).

Recent studies with a humanized anti-CD3 antibody in clinical trials suggested that this drug can induce regulatory CD8+ T cells. In this review, we discuss how these regulatory human CD8+ cells can be generated and the possible molecular tools they may use to inhibit immune responses. We compare our data on CD8+ regulatory cells induced by anti-CD3 stimulation with those reported in other experimental systems to identify both common and unique features of these cells.

RAGE ligation affects T cell activation and controls T cell differentiation.

The pattern recognition receptor, RAGE, has been shown to be involved in adaptive immune responses but its role on the components of these responses is not well understood. We have studied the effects of a small molecule inhibitor of RAGE and the deletion of the receptor (RAGE-/- mice) on T cell responses involved in autoimmunity and allograft rejection. Syngeneic islet graft and islet allograft rejection was reduced in NOD and B6 mice treated with TTP488, a small molecule RAGE inhibitor (p < 0.

Food microbial pathogen detection and analysis using DNA microarray technologies.

Culture-based methods used for microbial detection and identification are simple to use, relatively inexpensive, and sensitive. However, culture-based methods are too time-consuming for high-throughput testing and too tedious for analysis of samples with multiple organisms and provide little clinical information regarding the pathogen (e.g.

Imitative learning from a third-party interaction: relations with self-recognition and perspective taking.

Young children's ability to learn something new from a third-party interaction may be related to the ability to imagine themselves in the third-party interaction. This imaginative ability presupposes an understanding of self-other equivalence, which is manifested in an objective understanding of the self and an understanding of others' subjective perspectives. The current study measured imitative learning of a novel action seen only in a third-party interaction, mirror self-recognition, and perspective taking in a group of 48 18- to 20-month-olds.

Receptor for advanced glycation end products: fundamental roles in the inflammatory response: winding the way to the pathogenesis of endothelial dysfunction and atherosclerosis.

The multiligand receptor for advanced glycation end products (RAGE) of the immunoglobulin superfamily is expressed on multiple cell types implicated in the immune-inflammatory response and in atherosclerosis. Multiple studies have elucidated that ligand-RAGE interaction on cells, such as monocytes, macrophages, and endothelial cells, mediates cellular migration and upregulation of proinflammatory and prothrombotic molecules. In addition, recent studies reveal definitive rules for RAGE in effective T lymphocyte priming in vivo.

Prevention of type 1 diabetes: the time has come.

Improved understanding of the pathogenesis of type 1 diabetes mellitus has completely changed our view of this disease in the past 25 years-from an acute, fulminant disease, to a chronic, autoimmune process. Information on genetic and serologic markers has increased our ability to identify individuals at risk. Prospectively gathered data indicate that, with a combination of immunologic and metabolic studies, children with a 6-year risk of disease higher than 90% can be identified due to an ongoing immune process.

Receptor for AGE (RAGE): weaving tangled webs within the inflammatory response.

The family of RAGE ligands, including Advanced Glycation Endproducts (AGEs), S100/calgranulins, High Mobility Group Box-1 (HMGB1) and amyloid beta peptide (Abeta) and beta-sheet fibrils are highly enriched in immune and inflammatory foci. In parallel, upregulation of Receptor for AGE (RAGE) is noted in diverse forms of inflammation and autoimmunity, based on experiments examining human tissues as well as animal models. Indeed, prior to the demonstration that S100/calgranulins were signal transduction ligands of RAGE, these molecules were considered "biomarkers" of disease and disease activity in disorders such as colitis and arthritis.

RAGE: exacting a toll on the host in response to polymicrobial sepsis and Listeria monocytogenes.

The receptor for advanced glycation endproducts (RAGE) has complex roles in the immune/inflammatory response. RAGE is expressed on monocytes/macrophages, T and B lymphocytes, and dendritic cells. Previous studies illustrated that homozygous RAGE-/- mice subjected to overwhelming bacterial sepsis displayed normal clearance of pathogenic bacteria and significantly increased survival.

A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene.

Immunodeficient NOD-scid mice bearing a targeted mutation in the IL2 receptor common gamma chain (Il2rgamma(null)) readily engraft with human stem cells. Here we analyzed human peripheral blood mononuclear cells (PBMC) for their ability to engraft NOD-scid Il2rgamma(null) mice and established engraftment kinetics, optimal cell dose, and the influence of injection route. Even at low PBMC input, NOD-scid Il2rgamma(null) mice reproducibly support high human PBMC engraftment that plateaus within 3-4 weeks.

Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo.

Receptor for advanced glycation end products (RAGE) is an activation receptor triggered by inflammatory S100/calgranulins and high mobility group box-1 ligands. We have investigated the importance of RAGE on Ag priming of T cells in murine models in vivo. RAGE is inducibly up-regulated during T cell activation.

A patient with type B insulin resistance syndrome, responsive to immune therapy.

Background: A 55-year-old woman with vitiligo, hypothyroidism, interstitial lung disease and diabetes mellitus developed severe insulin resistance during a hospital admission for respiratory failure. Before hospitalization, her HbA(1c) level was 8.1% on approximately 100 U/day of insulin.

Type 1 diabetes as a relapsing-remitting disease?

Chronic immunological processes that underlie persistent viral infections and autoimmune disorders such as multiple sclerosis can be relapsing-remitting in nature. The progressive loss of beta-cell mass during the development of autoimmune type 1 diabetes (T1D) can also be non-linear, but the exact nature and kinetics of the immunological processes that govern T1D are not known. Here, we propose that the immunological process that is at the root of T1D is relapsing-remitting in nature and discuss the unresolved controversies and therapeutic implications of this hypothesis.

Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells.

Immune modulators can arrest loss of insulin secretion in type 1 diabetes mellitus (T1DM), but they have not caused permanent disease remission or restored normal insulin secretion. We tested whether exendin-4, a glucagon-like peptide-1 receptor agonist, would enhance remission of T1DM in NOD mice treated with anti-CD3 monoclonal antibody (mAb) and studied the effects of exendin-4 treatment on cellular and metabolic responses of beta-cells. Diabetic NOD mice treated with anti-CD3 mAb and exendin-4 had a higher rate of remission (44%) than mice treated with anti-CD3 mAb alone (37%) or exendin-4 (0%) or insulin or IgG alone (0%) (P < 0.

Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress.

The multiligand receptor for advanced glycation end products (RAGE) of the Ig superfamily transduces the biological impact of discrete families of ligands, including advanced glycation end products, certain members of the S100/calgranulin family, high mobility group box-1, Mac-1 (alpha(M)beta(2), CD11b/CD18), and amyloid-beta peptide and beta-sheet fibrils. Although structurally dissimilar, at least at the monomeric level, recent evidence suggests that oligomeric forms of these RAGE ligands may be especially apt to activate the receptor and up-regulate a program of inflammatory and tissue injury-provoking genes. The challenge in probing the biology of RAGE and its impact in acute responses to stress and the potential development of chronic disease is to draw the line between mechanisms that evoke repair versus those that sustain inflammation and tissue damage.

A scanning electron microscopy evaluation of microfractures, deformation and separation in EndoSequence and Profile nickel-titanium rotary files using an extracted molar tooth model.

The development of microfractures in the EndoSequence nickel-titanium rotary (NTR) file (Brassler USA, Savannah, GA) and Profile NTR file was evaluated by using scanning electron microscopy (SEM). Seventy-three maxillary buccal roots and 53 mandibular mesial roots with an average canal curvature of 37 degrees were randomly assigned to one of three groups and prepared with 21-mm .06 taper NTR files as follows: (1) EndoSequence at 300 rpm, (2) EndoSequence at 600 rpm, and (3) ProFile at 300 rpm.

Autoimmunity and beta cell regeneration in mouse and human type 1 diabetes: the peace is not enough.

Accumulating data from animal models of type 1 diabetes and some findings from clinical studies suggest that autoimmune destruction of islet beta cells is associated with enhanced beta cell regeneration. Successful immune therapies, aimed at preservation of islet cell mass, result in a remarkable reduction of beta cell regeneration. Treated or not, as long as the task of treatment is limited by "making peace" with autoimmunity, the process of beta cell loss continues.