CLAN, a Novel Human CED-4-like Gene

Proteins governing cell death form the basis of many normal processes and contribute to the pathogenesis of many diseases when dysregulated. Here we report the cloning of a novel human CED-4-like gene, CLAN, and several of its alternatively spliced isoforms. These caspase-associated recruitment domain (CARD)-containing proteins are expressed at varying degrees in normal human tissues and may contribute to a number of intracellular processes including apoptosis, cytokine processing, and NF-κB activation. The CARD of the CLAN proteins binds a number of other CARD-containing proteins including caspase-1, BCL10, NOD2, and NAC. Once their physiologic functions are uncovered, CLAN proteins may prove to be valuable therapeutic targets.     

Stability and change in genetic and environmental influences on hand-grip strength in older male twins.

The aim of this study was to investigate aging-related changes in the contribution of genetic and environmental influences to hand-grip strength in late adulthood. Subjects in this study are 152 intact twin pairs (77 monozygotic and 75 dizygotic pairs) from the National Heart, Lung, and Blood Institute Twin Study assessed repeatedly for hand-grip strength at mean ages of 63 and 73 yr. Structural equation genetic modeling was used to investigate stability and change in the genetic and environmental components of variance of hand-grip strength in late adulthood. Average decline in strength over the 10 yr of follow-up was -1.05+/-6.8 (SD) kg and was highly significant (P = 0.003). The test-retest correlation between baseline and follow-up grip strength was 0.62 (P<0.001). Bivariate genetic modeling found significant genetic and shared environmental stability in hand-grip strength over the 10 yr of follow-up, with genetic and shared environmental influences accounting for 35 and 48%, respectively, of the test-retest phenotypic correlation. We conclude from these results that stability in hand-grip strength in late adulthood is due primarily to continuity of genetic and familial influences.     

Activation of superoxide production and differential exocytosis in polymorphonuclear leukocytes by cytochalasins A,B, C,D and E: Effects of various ions

All of the common cytochalasins activate superoxide anion release and exocytosis of β-N-acetylglucosaminidase and lysozyme from guinea-pig polymorphonuclear leukocytes (neutrophils) incubated in a buffered sucrose medium. Half-maximal activation of both processes is produced by approx. 2 μM cytochalasin A, C >μM cytochalasin B ? 4–5 μM cytochalasin D, E. While maximal rates of O₂^? release and extents of exocytosis require extracellular calcium (1–2 mM), replacing sucrose with monovalent cation chlorides is inhibitory to neutrophil activation by cytochalasins. Na⁺, K⁺ or choline inhibited either cytochalasin B- or E-stimulated O₂^? production with IC₅₀ values of 5–10 mM and inhibition occurs whether Cl^?, NO₃^? or SCN^? is the anion added with Na⁺ or K⁺. Release of β-N-acetylglucosaminidase in control or cytochalasin B-stimulated cells is inhibited by NaCl (IC₅₀ ≈ 10 mM), while cytochalasin E-stimulated exocytosis is reduced less and K⁺ or choline chloride are ineffective in inhibiting either cytochalasin B- or E-stimulated exocytosis. Release of β-glucuronidase, myeloperoxidase or acid phosphatase from neutrophils incubated in buffered sucrose is not stimulated by cytochalasin B. Stimulation of either O₂^? or β-N-acetylglucosaminidase release by low concentrations of cytochalasin A is followed by inhibition of each at higher concentrations. It appears that all cytochalasins can activate both NAD(P)H oxidase and selective degranulation of neutrophils incubated in salt-restricted media and that differential inhibition of these two processes by monovalent cations and/or anions is produced at some step(s) subsequent to cytochalasin interaction with the cell.