Management of sudden cardiac death in cardiac sarcoidosis using the wearable cardioverter defibrillator.

Background: Patients with cardiac sarcoidosis are at increased risk of ventricular tachycardia/fibrillation.

Objective: We tested the hypothesis that the wearable cardioverter defibrillator can be used to mitigate the risk of sudden cardiac death among cardiac sarcoidosis patients.

Methods: A retrospective review of the commercial database identified cardiac sarcoidosis patients who wore the wearable cardioverter defibrillator.

Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death.

Background: This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation.

Methods: From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers.

Pro-Inflammatory Cytokines Predict Relapse-Free Survival after One Month of Interferon-α but Not Observation in Intermediate Risk Melanoma Patients.

Background: E1697 was a phase III trial of adjuvant interferon (IFN)-α2b for one month (Arm B) versus observation (Arm A) in patients with resected melanoma at intermediate risk. We evaluated the levels of candidate serum cytokines, the HLA genotype, polymorphisms of CTLA4 and FOXP3 genes and the development of autoantibodies for their association with relapse free survival (RFS) in Arm A and Arm B among 268 patients with banked biospecimens.

Methods: ELISA was used to test 5 autoantibodies.

ATF4 protein deficiency protects against high fructose-induced hypertriglyceridemia in mice.

Hypertriglyceridemia is the most common lipid disorder in obesity and type 2 diabetes. It results from increased production and/or decreased clearance of triglyceride-rich lipoproteins. To better understand the pathophysiology of hypertriglyceridemia, we studied hepatic regulation of triglyceride metabolism by the activating transcription factor 4 (ATF4), a member of the basic leucine zipper-containing protein subfamily.

Clustering and alignment of polymorphic sequences for HLA-DRB1 genotyping.

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants.

FoxO6 integrates insulin signaling with gluconeogenesis in the liver.

Objective: Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism.

Targeting FoxO1 for hypertriglyceridemia.

Hypertriglyceridemia is characterized by increased production and decreased clearance of triglyceride-rich lipoproteins including very low-density lipoprotein (VLDL) and chylomicron. Due to its proatherogenic profile, hypertriglyceridemia contributes to the development of atherosclerosis and coronary artery disease. While the pathophysiology of hypertriglyceridemia remains poorly understood, its close association with obesity and type 2 diabetes implicates insulin resistance in the pathogenesis of hypertriglyceridemia.

Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies.

We propose a method to analyze family-based samples together with unrelated cases and controls. The method builds on the idea of matched case-control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo-controls are constructed, based upon the transmitted and untransmitted alleles.

FoxO1 links hepatic insulin action to endoplasmic reticulum stress.

Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. Hepatic FoxO1 activity is up-regulated to promote glucose production during fasting and is suppressed to limit postprandial glucose excursion after meals. Increased FoxO1 activity augments the expression of insulin receptor (IR) and IR substrate (IRS)2, which in turn inhibits FoxO1 activity in response to reduced insulin action.

Screen and clean: a tool for identifying interactions in genome-wide association studies.

Epistasis could be an important source of risk for disease. How interacting loci might be discovered is an open question for genome-wide association studies (GWAS). Most researchers limit their statistical analyses to testing individual pairwise interactions (i.

Multiplex HLA-typing by pyrosequencing.

Class I and II loci of the human leukocyte antigens (HLA) represent the most polymorphic region of the genome. Evolutionary pressure has resulted in a large number of allelic variants of these loci ensuring the high frequency of heterozygous genotypes observed in human populations. Molecular techniques, including sequencing, are capable of precisely defining HLA alleles.

A single mutation in the IF3 N-terminal domain perturbs the fidelity of translation initiation at three levels.

Bacterial translation initiation factor 3 (IF3) is involved in the fidelity of translation initiation at several levels, including start-codon discrimination, mRNA translation, and initiator-tRNA selection. The IF3 C-terminal domain (CTD) is required for binding to the 30S ribosomal subunit. N-terminal domain (NTD) function is less certain, but likely contributes to initiation fidelity.

Proteomic analysis of fructose-induced fatty liver in hamsters.

High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia.

On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants.

Resources being amassed for genome-wide association (GWA) studies include "control databases" genotyped with a large-scale SNP array. How to use these databases effectively is an open question. We develop a method to match, by genetic ancestry, controls to affected individuals (cases).

Quantification of CpG island methylation in progressive breast lesions from normal to invasive carcinoma.

Epigenetic silencing of specific genes is associated with cancer progression. CpG islands are present at higher frequency in promoter regions, their methylation leading to gene underexpression. Pyrosequencing provides sequencing analysis of genetic markers, e.

Pyrosequencing-based strategies for improved allele typing of human leukocyte antigen loci.

Successful transplantation of tissue during solid organ and bone marrow transplantation relies on accurate determination of the human leukocyte antigen (HLA) phenotype of the potential donor(s) and recipient. Matching donor with recipient for a kidney transplant generally means finding a six-antigen match by looking at each of two alleles at HLA-A, -B, and -DR loci. For bone marrow transplantation the HLA-C and -DQ alleles are also considered.

Web-based primer design software for genome-scale genotyping by pyrosequencing.

Design of locus-specific primers for use during genetic analysis requires combining information from multiple sources and can be a time-consuming process when validating large numbers of assays. Data warehousing of genomic DNA sequences and genetic variations when coupled with software applications for optimizing the generation of locus-specific primers can increase the efficiency of assay development. Selection of oligonucleotide primers for PCR and Pyrosequencing (SOP3) software allows user-directed queries of warehoused data collected from the human and mouse genome sequencing projects.

Rehabilitation of adaptive immunity and regeneration of beta cells.

Type 1 Diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic insulin-producing beta cells that most frequently occurs in genetically predisposed children. Recent observations illustrating the regenerative capability of the endocrine pancreas in addition to advances in stem cell and gene therapy technologies enable the exploration of alternatives to allogeneic islet transplantation. Living-cell-mediated approaches can abrogate autoimmunity and the consequent destruction of beta cells without the need for immunosuppressive drugs.

SOP3v2: web-based selection of oligonucleotide primer trios for genotyping of human and mouse polymorphisms.

SOP3v2 is a database-driven graphical web-based application for facilitating genotyping assay design. SOP3v2 accepts data input in numerous forms, including gene names, reference sequence numbers and physical location. For each entry, the application presents a set of recommended forward and reverse PCR primers, along with a sequencing primer, which is optimized for sequence-based genotyping assays.

Regenerative medicine for diabetes treatment.

Extract: Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta-cells contained within the pancreatic islet of Langerhans are destroyed by autoreactive T cells. T1D patients are treated via insulin hormone replacement therapy by subcutaneous injection of recombinant insulin (produced by molecular engineering). Blood glucose levels must be monitored many times a day to determine the appropriate quantity of insulin to be injected in order to control blood glucose levels (glycemia).

SOP3: a web-based tool for selection of oligonucleotide primers for single nucleotide polymorphism analysis by Pyrosequencing.

SOP3 is a web-based software tool for designing oligonucleotide primers for use in the analysis of single nucleotide polymorphisms (SNPs). Accessible via the Internet, the application is optimized for developing the PCR and sequencing primers that are necessary for Pyrosequencing. The application accepts as input gene name, SNP reference sequence number, or chromosomal nucleotide location.

High-throughput polyribosome fractionation.

Polyribosome sedimentation velocity centrifugation can be used to identify differential regulation of the translation of mRNAs. However, ultracentrifugation presents practical limitations on the number of sedimentation velocity gradients that can be run simultaneously. A method for sedimentation velocity analysis of polyribosomes is presented that is based on low-speed centrifugation of sucrose gradients prepared in deep 96-well plates, the advantage of which is that hundreds of polyribosome fractionations can be performed simultaneously in a tabletop centrifuge.

HLA class II DRB high resolution genotyping by pyrosequencing: comparison of group specific PCR and pyrosequencing primers.

Sequencing of alleles of the highly polymorphic, multiple loci HLA-DRB gene family was performed by pyrosequencing using purified DNA from the 11(th) International Histocompatibility Workshop human lymphoblastiod cell lines as well as genomic DNA isolated from blood samples obtained from healthy adult volunteers. Genomic DNA was prepared from donors whose blood had been stored either frozen or as dried blood spots. Pyrosequence-based typing was optimized for identifying alleles of the HLA-DRB1, -3, -4, and -5 genes.