Effectiveness of screening older people for impaired vision in community setting: systematic review of evidence from randomised controlled trials

Objective: To assess whether population screening for impaired vision among older people in the community leads to improvements in vision.

Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors

Oxidants generated by eosinophils during chronic inflammation may lead to mutagenesis in adjacent epithelial cells. Eosinophil peroxidase, a heme enzyme released by eosinophils, generates hypobromous acid that damages tissue in inflammatory conditions. We show that human eosinophils use eosinophil peroxidase to produce 5-bromodeoxycytidine. Flow cytometric, immunohistochemical, and mass spectrometric analyses all demonstrated that 5-bromodeoxycytidine generated by eosinophil peroxidase was taken up by cultured cells and incorporated into genomic DNA as 5-bromodeoxyuridine. Although previous studies have focused on oxidation of chromosomal DNA, our observations suggest another mechanism for oxidative damage of DNA. In this scenario, peroxidase-catalyzed halogenation of nucleotide precursors yields products that subsequently can be incorporated into DNA. Because the thymine analog 5-BrUra mispairs with guanine in DNA, generation of brominated pyrimidines by eosinophils might constitute a mechanism for cytotoxicity and mutagenesis at sites of inflammation.

A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation

We have identified a human cytomegalovirus cell-death suppressor, denoted vICA, encoded by the viral UL36 gene. vICA inhibits Fas-mediated apoptosis by binding to the pro-domain of caspase-8 and preventing its activation. vICA does not share significant sequence homology with FLIPs or other known suppressors of apoptosis, suggesting that this protein represents a new class of cell-death suppressors. Notably, resistance to Fas-mediated apoptosis is delayed in fibroblasts infected with viruses that encode mutant vICA, suggesting that vICA suppresses death-receptor-induced cell death in the context of viral infection. Although vICA is dispensable for viral replication in vitro, the common targeting of caspase-8 activation by diverse herpesviruses argues for an important role for this antiapoptotic mechanism in the pathogenesis of viral infection in the host, most likely in avoiding immune clearance by cytotoxic lymphocytes and natural killer cells.

Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when coligated with the high-affinity Fc receptor for IgE.

Mouse mast cells express gp49B1, a cell-surface member of the Ig superfamily encoded by the gp49B gene. We now report that by ALIGN comparison of the amino acid sequence of gp49B1 with numerous receptors of the Ig superfamily, a newly recognized family has been established that includes gp49B1, the human myeloid cell Fc receptor for IgA, the bovine myeloid cell Fc receptor for IgG2, and the human killer cell inhibitory receptors expressed on natural killer cells and T lymphocyte subsets. Furthermore, the cytoplasmic domain of gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs that are also present in killer cell inhibitory receptors; these motifs downregulate natural killer cell and T-cell activation signals that lead to cytotoxic activity. As assessed by flow cytometry with transfectants that express either gp49B1 or gp49A, which are 89% identical in the amino acid sequences of their extracellular domains, mAb B23.1 was shown to recognize only gp49B1. Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. Thus, gp49B1 is an immunoreceptor tyrosine-based inhibition motif-containing integral cell-surface protein that downregulates the high-affinity Fc receptor for IgE-mediated release of proinflammatory mediators from mast cells. Our findings establish a novel counterregulatory transmembrane pathway by which mast cell activation can be inhibited.

The N gene of tobacco confers resistance to tobacco mosaic virus in transgenic tomato.

It has been proposed that cloned plant disease resistance genes could be transferred from resistant to susceptible plant species to control important crop plant diseases. The recently cloned N gene of tobacco confers resistance to the viral pathogen, tobacco mosaic virus. We generated transgenic tomato plants bearing the N gene and demonstrate that N confers a hypersensitive response and effectively localizes tobacco mosaic virus to sites of inoculation in transgenic tomato, as it does in tobacco. The ability to reconstruct the N-mediated resistance response to tobacco mosaic virus in tomato demonstrates the utility of using isolated resistance genes to protect crop plants from diseases, and it demonstrates that all the components necessary for N-mediated resistance are conserved in tomato.

A role for Rho in Ras transformation.

The small GTP-binding proteins Rac and Rho are key elements in the signal-transduction pathways respectively controlling the formation of lamellipodia and stress fibers induced by growth factors or oncogenic Ras. We recently reported that Rac function is necessary for Ras transformation and that expression of constitutively activated Rac1 is sufficient to cause malignant transformation. We now show that, although expression of constitutively activated V14-RhoA in Rat 1 fibroblasts does not cause transformation on its own, it strongly cooperates with constitutively active RafCAAX in focus-formation assays in NIH 3T3 cells. Furthermore, dominant-negative N19-RhoA inhibits focus formation by V12-H-Ras and RafCAAX in NIH 3T3 cells, and stable coexpression of N19-RhoA and V12-H-Ras in Rat1 fibroblasts reverts Ras transformation. Interestingly, stress fiber formation is inhibited in V12-H-Ras lines and restored by coexpression of N19-RhoA. We conclude that Rho drives at least two separate pathways, one that induces stress fiber formation and another one that is important for transformation by oncogenic Ras.

Mutagenesis of the human apolipoprotein B gene in a yeast artificial chromosome reveals the site of attachment for apolipoprotein(a).

Lipoprotein(a) [Lp(a)] is a lipoprotein formed by the disulfide linkage of apolipoprotein (apo) B100 of a low density lipoprotein particle to apolipoprotein(a). Prior studies have suggested that one of the C-terminal Cys residues of apo-B100 is involved in the disulfide linkage of apo-B100 to apo(a). To identify the apo-B100 Cys residue involved in the formation of Lp(a), we constructed a yeast artificial chromosome (YAC) spanning the human apo-B gene and used gene-targeting techniques to change Cys-4326 to Gly. The mutated YAC DNA was used to generate transgenic mice expressing the mutant human apo-B100 (Cys4326Gly). Unlike the wild-type human apo-B100, the mutant human apo-B100 completely lacked the ability to bind to apo(a) and form Lp(a). This study demonstrates that apo-B100 Cys-4326 is required for the assembly of Lp(a) and shows that gene targeting in YACs, followed by the generation of transgenic mice, is a useful approach for analyzing the structure of large proteins coded for by large genes.

Diseño y análisis comparativo de un inventario de indicadores de mortalidad evitable adaptado a las condiciones sanitarias de Colombia

Objetivos. Elaborar un inventario de indicadores de mortalidad evitable (INIME) que permita analizar las fallas en el control de los riesgos de mortalidad predominantes en Colombia y comparar los resultados de su aplicación con los obtenidos mediante dos enfoques ampliamente utilizados. Métodos. Se revisaron los registros oficiales de mortalidad de Colombia de 1985 a 2001; las causas básicas de muerte se clasificaron según la CIE-9. Se seleccionaron los indicadores de mortalidad evitable (ME) mediante un algoritmo que combinó las listas de Holland y de Taucher, la definición de Rutstein y colaboradores y el principio de Uemura. Se compararon las proporciones de muertes evitables resultantes de aplicar el INIME y las dos listas de ME a una base de datos con los registros oficiales de defunciones de Colombia de 1993 a 1996. Resultados. De las 680 617 defunciones registradas en el período de estudio, se clasificaron como evitables 18,2% según la lista de Holland y 51,3% según la lista de Taucher. La ME según el INIME ascendió a 76,7%. Este patrón se mantuvo relativamente estable entre 1993 y 1996. Las diferencias observadas en la proporción de muertes evitables según el INIME y las dos listas de ME se relacionaron con el perfil epidemiológico local y el enfoque conceptual de cada lista. Conclusiones. Las diferencias entre el INIME y las listas de ME de Holland y de Taucher muestran las consecuencias de usar una u otra clasificación en el contexto colombiano. El INIME puede constituir un recurso valioso para fundamentar y evaluar políticas sanitarias, pero debe ajustarse a la situación específica en que se aplique.

Catharine Waugh McCullouch papers in the Mary Earhart Dillon collection, 1869-1945

Collection primarily documents McCulloch's research on women's legal status, and her work with the Illinois Equal Suffrage Association, the National American Woman Suffrage Association, and the League of Women Voters. There is also documentation of women in the legal profession, of McCulloch's friendships with the other women suffragists and lawyers, and some biographical material. The papers contain little information about her family or social life.

The State of the Union(s): The Eurozone Crisis, Comparative Regional Integration and the EU Model

No abstract.

2004 University of Michigan Baseball Team

Top Row: (10) Chris Getz, Derek Feldkamp, Michael Penn, Andrew Hess, Brandon Roberts, Michael McCormick, Ali Husain, Jim Brauer, Steve Boge, Jeff Niemiec.

3rd Row: (8) Student Manager Chris Clark, Alan Ulrich, Leif Mahler, Phil Tognetti, Lentz., Kyle Bohm, Matt Petry, Dan Lentz, Craig Murray, Student Manager Jason Brin

2nd Row: Brad Seddon, Matt Rademacher, Bobby Garza, Assistant Coach Jason Murray Head Coach Rich Maloney, Assistant Coach Scott Mallernee, Jeremy Goldschmeding, Brad Roblin, Jeff Kunkel.

Front Row: (8, Sitting) Matt Butler, A.]. Scheidt, Nick Rudden, Eric Rose, Chris Burh Paul Hammond, Matt Petry, Mike Schmidt.

Missing: Assistant Coach John Lowery, Drew Taylor (Injured), Matt Clark, Tyler Ca