67 research outputs found

    Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content.

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    OBJECTIVE: We tested the primary hypotheses that sphingolipid and diacylglycerol (DAG) content is higher within insulin-resistant muscle and that the association between intramyocellular triglycerides (IMTG) and insulin resistance is muscle fiber type specific. RESEARCH DESIGN AND METHODS: A nested case-control analysis was conducted in 22 obese (BMI >30 kg/m(2)) women who were classified as insulin-resistant (IR; n = 12) or insulin-sensitive (IS; n = 10), determined by hyperinsulinemic-euglycemic clamp (>30% greater in IS compared with IR, P < 0.01). Sphingolipid and DAG content was determined by high-performance liquid chromatography-tandem mass spectrometry. Fiber type-specific IMTG content was histologically determined. Gene expression was determined by quantitative PCR. RESULTS: Total (555 +/- 53 vs. 293 +/- 54 pmol/mg protein, P = 0.004), saturated (361 +/- 29 vs. 179 +/- 34 pmol/mg protein, P = 0.001), and unsaturated (198 +/- 29 vs. 114 +/- 21 pmol/mg protein, P = 0.034) ceramides were higher in IR compared with IS. DAG concentrations, however, were similar. IMTG content within type I myocytes, but not type II myocytes, was higher in IR compared with IS subjects (P = 0.005). Insulin sensitivity was negatively correlated with IMTG within type I myocytes (R = -0.51, P = 0.026), but not with IMTG within type II myocytes. The proportion of type I myocytes was lower (41 vs. 59%, P < 0.01) in IR subjects. Several genes involved in lipid droplet and fatty acid metabolism were differentially expressed in IR compared with IS subjects. CONCLUSIONS: Human skeletal muscle insulin resistance is related to greater IMTG content in type I but not type II myocytes, to greater ceramide content, and to alterations in gene expression associated with lipid metabolism

    Inter-rater reliability of the EPUAP pressure ulcer classification system using photographs

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    Background. Many classification systems for grading pressure ulcers are discussed in the literature. Correct identification and classification of a pressure ulcer is important for accurate reporting of the magnitude of the problem, and for timely prevention. The reliability of pressure ulcer classification systems has rarely been tested. Aims and objectives. The purpose of this paper is to examine the inter-rater reliability of classifying pressure ulcers according to the European Pressure Ulcer Advisory Panel classification system when using pressure ulcer photographs.Design. Survey was among pressure ulcer experts.Methods. Fifty-six photographs were presented to 44 pressure ulcer experts. The experts classified the lesions as normal skin, blanchable erythema, pressure ulcer (four grades) or incontinence lesion. Inter-rater reliability was calculated.Results. The multirater-Kappa for the entire group of experts was 0.80 (P < 0.001).Various groups of experts obtained comparable results. Differences in classifications are mainly limited to 1 degree of difference. Incontinence lesions are most often confused with grade 2 (blisters) and grade 3 pressure ulcers (superficial pressure ulcers).Conclusions. The inter-rater reliability of the European Pressure Ulcer Advisory Panel classification appears to be good for the assessment of photographs by experts. The difference between an incontinence lesion and a blister or a superficial pressure ulcer does not always seem clear.Relevance to clinical practice. The ability to determine correctly whether a lesion is a pressure ulcer lesion is important to assess the effectiveness of preventive measures. In addition, the ability to make a correct distinction between pressure ulcers and incontinence lesions is important as they require different preventive measures. A faulty classification leads to mistaken measures and negative results. Photographs can be used as a practice instrument to learn to discern pressure ulcers from incontinence lesions and to get to know the different grades of pressure ulcers. The Pressure Ulcer Classification software package has been developed to facilitate learning

    Hidden Order in the Cuprates

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    We propose that the enigmatic pseudogap phase of cuprate superconductors is characterized by a hidden broken symmetry of d(x^2-y^2)-type. The transition to this state is rounded by disorder, but in the limit that the disorder is made sufficiently small, the pseudogap crossover should reveal itself to be such a transition. The ordered state breaks time-reversal, translational, and rotational symmetries, but it is invariant under the combination of any two. We discuss these ideas in the context of ten specific experimental properties of the cuprates, and make several predictions, including the existence of an as-yet undetected metal-metal transition under the superconducting dome.Comment: 12 pages of RevTeX, 9 eps figure

    A Combinatorial Partitioning Method to Identify Multilocus Genotypic Partitions That Predict Quantitative Trait Variation

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    Recent advances in genome research have accelerated the process of locating candidate genes and the variable sites within them and have simplified the task of genotype measurement. The development of statistical and computational strategies to utilize information on hundreds — soon thousands — of variable loci to investigate the relationships between genome variation and phenotypic variation has not kept pace, particularly for quantitative traits that do not follow simple Mendelian patterns of inheritance. We present here the combinatorial partitioning method (CPM) that examines multiple genes, each containing multiple variable loci, to identify partitions of multilocus genotypes that predict interindividual variation in quantitative trait levels. We illustrate this method with an application to plasma triglyceride levels collected on 188 males, ages 20–60 yr, ascertained without regard to health status, from Rochester, Minnesota. Genotype information included measurements at 18 diallelic loci in six coronary heart disease–candidate susceptibility gene regions: APOA1-C3-A4, APOB, APOE, LDLR, LPL, and PON1. To illustrate the CPM, we evaluated all possible partitions of two-locus genotypes into two to nine partitions (∼10(6) evaluations). We found that many combinations of loci are involved in sets of genotypic partitions that predict triglyceride variability and that the most predictive sets show nonadditivity. These results suggest that traditional methods of building multilocus models that rely on statistically significant marginal, single-locus effects, may fail to identify combinations of loci that best predict trait variability. The CPM offers a strategy for exploring the high-dimensional genotype state space so as to predict the quantitative trait variation in the population at large that does not require the conditioning of the analysis on a prespecified genetic model

    Apolipoprotein H (beta-2-glycoprotein I) polymorphism in Asians.

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    Human Biology644617-62

    Apolipoprotein H (Beta-2-Glycoprotein I) Polymorphism in Asians

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    Apolipoprotein H (APOH) (beta-2-glycoprotein I) polymorphism has been studied in 1159 Asian s. The sample included 872 Chinese, 179 Asiatic Indians (Dravidian), 91 Filipinos,and 17 Malays. APOH polymorphism was determined by isoelectric focusing of sera in thin-layer polyacrylamide gels containing 3 M urea followed by immunoblotting. The frequencies of the three alleles— APOH*l, APOH*2, and APOH*3--were found to be 0.031, 0.900, and 0.069 in the Chinese; 0.061, 0.866, and 0.073 in the Dravidian Indians; 0.055, 0.923, and 0.022 in the Filipinos; and 0.088, 0.882, and 0.029 in the Malays. The phenotypic distribution was at Hardy -Weinberg equilibrium in all the populations
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