Biased Immunoglobulin Light Chain Gene Usage in the Shark.

This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined).

Applications of temporal kernel canonical correlation analysis in adherence studies.

Adherence to medication is often measured as a continuous outcome but analyzed as a dichotomous outcome due to lack of appropriate tools. In this paper, we illustrate the use of the temporal kernel canonical correlation analysis (tkCCA) as a method to analyze adherence measurements and symptom levels on a continuous scale. The tkCCA is a novel method developed for studying the relationship between neural signals and hemodynamic response detected by functional MRI during spontaneous activity.

Gastric electrical stimulation treatment of type 2 diabetes: effects of implantation versus meal-mediated stimulation. A randomized blinded cross-over trial.

Gastric electrical stimulation with the implanted DIAMOND device has been shown to improve glycemic control and decrease weight and systolic blood pressure in patients with type 2 diabetes inadequately controlled with oral antidiabetic agents. The objective of this study was to determine if device implantation alone (placebo effect) contributes to the long-term metabolic benefits of DIAMOND(®) meal-mediated gastric electrical stimulation in patients with type 2 diabetes. The study was a 48 week randomized, blinded, cross-over trial in university centers comparing glycemic improvement of DIAMOND(®) implanted patients with type 2 diabetic with no activation of the electrical stimulation (placebo) versus meal-mediated activation of the electrical signal.

Treatment of Patients with Obese Type 2 Diabetes with Tantalus-DIAMOND® Gastric Electrical Stimulation: Normal Triglycerides Predict Durable Effects for at Least 3 Years.

The objectives of the present work are to evaluate long-term benefit of nonexcitatory gastric electrical stimulation (GES) by the DIAMOND(®) device on glycemic control and body weight in patients with type 2 diabetes inadequately controlled with oral agents and to determine the magnitude of the modulating effects of fasting plasma triglyceride (FTG) levels on these effects of GES. Sixty one patients with type 2 diabetes [HbA1c > 7.0% (53 mmol/mol) to < 10.

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

Objective: The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.

Research Design And Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.

The DIAMOND system in the treatment of type 2 diabetes mellitus in an obese patient.

Obesity and type 2 diabetes mellitus have reached epidemic proportions worldwide. As the majority of antidiabetic medications are of limited efficacy and patient adherence to long-term therapy is one of the main limiting factors of effective blood glucose and body weight control, new therapies are still looked for. The DIAMOND system seems to be one of the most promising among them.

Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.

Objective: Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status.

Research Design And Methods: A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.

Pyogenic Liver Abscess, Bacteremia, and Meningitis with Hypermucoviscous Klebsiella pneumoniae: An Unusual Case Report in a Human T-Cell Lymphotropic Virus Positive Patient of Caribbean Origin in the United States.

Pyogenic liver abscess (PLA) is a potentially fatal disease. Klebsiella pneumoniae (K. pneumoniae) has replaced Escherichia coli (E.

Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis.

Enterovirus 71 (EV71; family Picornaviridae, species human Enterovirus A) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. We investigated extra-central nervous system (extra-CNS) tissues capable of supporting EV71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor B2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL-1). Formalin-fixed, paraffin-embedded CNS and extra-CNS tissues from seven autopsy cases were examined by IHC and in situ hybridization to evaluate viral antigens and RNA.

Shark IgW C region diversification through RNA processing and isotype switching.

Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte Ag receptors generated by V(D)J recombination. Shark B cells express two classical Igs, IgM and IgW, encoded by an early, alternative gene organization consisting of numerous autonomous miniloci, where the individual gene cluster carries a few rearranging gene segments and one C region, μ or ω. We have characterized eight distinct Ig miniloci encoding the nurse shark ω H chain.

Autoimmune polyglandular syndromes: interplay between the immune and the endocrine systems leading to a diverse set of clinical diseases and new insights into immune regulation.

During the last 50 years, three major classes of autoimmune polyglandular syndromes (APSs) have been defined, and their characteristics and heritability have been delineated. Simultaneously, studies of the immunologic bases of these syndromes provided fundamental information in understanding immune regulation. Genetic analyses of patients and their families with APS type 1 (autoimmune polyendocrinopathy candidiasis, ectodermal dystrophy) identified the autoimmune regulator (AIRE) gene, which drives the expression of peripheral tissue-specific antigens in thymic cells and is critical in the development of self-tolerance.

Metabolic surgery for type 2 diabetes with BMI <35 kg/m(2) : an endocrinologist's perspective.

Is bariatric surgery as primary therapy for type 2 diabetes mellitus (T2DM) with body mass index (BMI) <35 kg/m(2) justified? Open-label studies have shown that bariatric surgery causes remission of diabetes in some patients with BMI <35 kg/m(2). All such patients treated had substantial weight loss. Diabetes remission was less likely in patients with lower BMI than those with higher BMI, in patients with longer than shorter duration and in patients with lesser than greater insulin reserve.

Fasting plasma triglycerides predict the glycaemic response to treatment of type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm.

Background: Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level.

Translational control at the synapse: role of RNA regulators.

Translational control of gene expression is instrumental in the regulation of eukaryotic cellular form and function. Neurons in particular rely on this form of control because their numerous synaptic connections need to be independently modulated in an input-specific manner. Brain cytoplasmic (BC) RNAs implement translational control at neuronal synapses.

Pramlintide: profile of an amylin analog.

Amylin is a naturally occurring hormone that regulates food intake and postprandial glucose excursions. Amylin is synthesized in the β cell and cosecreted with insulin. Type 1 diabetes and insulin-requiring Type 2 diabetes are amylin-deficient as well as insulin-deficient states.

Science, clinical outcomes and the popularization of diabetes surgery.

Purpose Of Review: Bariatric surgery is an important option for the treatment of severe (type III) obesity. Its role in the management of type 2 diabetes in overweight and obese patients needs to be defined.

Recent Findings: Intensified medical therapy can achieve target metabolic goals in many but not all patients with type 2 diabetes.

Non-insulin injectable treatments (glucagon-like peptide-1 and its analogs) and cardiovascular disease.

Glucagon-like peptide-1 (GLP-1) [GLP-1 (7-36)-amide] plays a fundamental role in regulating postprandial nutrient metabolism. GLP-1 acts through a G-protein-coupled receptor present on the membranes of many tissues, including myocardium and endothelium. GLP-1 is cleaved by the dipeptidyl peptidase-4 enzyme to its metabolite GLP-1 (9-36)-amide within 1-2 min of its release into the circulation.

Strongyloidiasis: a diagnosis more common than we think.

Strongyloides stercoralis is endemic to many tropical regions; however, there is limited knowledge concerning the clinical implication of this helminth, particularly in urban medical centers. We report a case series of strongyloidiasis in our urban medical center in New York City. Patients over the age of 18 years who were examined in our institution from January 1998 to May 2011 were identified by electronic medical record search using International Classification of Diseases, 9th Revision codes.

Origin of immunoglobulin isotype switching.

Background: From humans to frogs, immunoglobulin class switching introduces different effector functions to antibodies through an intrachromosomal DNA recombination process at the heavy-chain locus. Although there are two conventional antibody classes (IgM, IgW) in sharks, their heavy chains are encoded by 20 to >100 miniloci. These representatives of the earliest jawed vertebrates possess a primordial immunoglobulin gene organization where each gene cluster is autonomous and contains a few rearranging gene segments (VH-D1-D2-JH) with one constant region, μ or ω.

An isolated neurofibromal polyp of the colon.

Solitary neurofibromal colonic polyps are a rare entity, particularly outside the setting of neurofibromatosis type 1. The clinical significance of such lesions has not yet been established. Though typically benign tumors, neurofibromas have been reported to undergo malignant transformation, with an increased risk of malignancy when associated with neurofibromatosis.