Identification and evaluation of candidate genes for inherited retinal -degenerative diseases

Although more than 100 genes associated with inherited retinal disease have been mapped to chromosomal locations, less than half of these genes have been cloned. This text includes identification and evaluation of candidate genes for three autosomal dominant forms of inherited retinal degeneration: atypical vitelliform macular dystrophy (VMD1), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP). ^ VMD1 is a disorder characterized by complete penetrance but extremely variable expressivity, and includes macular or peripheral retinal lesions and peripappilary abnormalitites. In 1984, linkage was reported between VMD1 and soluble glutamate-pyruvate transaminase GPT); however, placement of GPT to 8q24 on linkage maps had been debated, and VMD1 did not show linkage to microsatellite markers in that region. This study excluded linkage between the loci by cloning GPT, identifying the nucleotide substitution associated with the GPT sozymes, and by assaying VMD1 family samples with an RFLP designed to detect the substitution. In addition, linkage of VMD1 to the known dominant macular degeneration loci was excluded. ^ CORD is characterized by early onset of color-vision deficiency, and decreased visual acuity, However, this retinal degeneration progresses to no light perception, severe macular lesion, and “bone-spicule” accumulations in the peripheral retina. In this study, the disorder in a large Texan family was mapped to the CORD2 locus of 19q13, and a mutation in the retina/pineal-specific cone-rod homeobox gene (CRX) was identified as the disease cause. In addition, mutations in CRX were associated with significantly different retinal disease phenotypes, including retinitis pigmentosa and Leber congenital amaurosis. ^ Many of the mutations leading to inherited retinal disorders have been identified in genes like CRX, which are expressed predominantly in the retina and pineal gland. Therefore, a combination of database analysis and laboratory investigation was used to identify 26 novel retina/pineal-specific expressed sequence tag (EST) clusters as candidate genes for inherited retinal disorders. Eight of these genes were mapped into the candidate regions of inherited retinal degeneration loci. ^ Two of the eight clusters mapped into the retinitis pigmentosa RP13 candidate region of 17p13, and were both determined to represent a single gene that is highly expressed in photoreceptors. This gene, the Ah receptor-interacting like protein-1 (AIPL1), was cloned, characterized, and screened for mutations in RP13 patient DNA samples. ^

Characterization of anti -sulfatide autoantibodies in demyelinating diseases

Multiple sclerosis (MS) is the most common autoimmune disease of the central nerve system and Guillain Barré Syndrome (GBS) is an inflammatory neuropathy involving the peripheral nerves. Anti-myelin immunoglobins may play a role in the demyelination processes of the both diseases. Sulfatide is an abundant glycolipid on myelin and is a candidate target antigen for disease related autoantibodies. The objective of this study was to characterize anti-sulfatide antibodies and compare antibodies from GBS and MS patients with fetal antibodies. Our hypothesis is that some B cells producing disease-associated autoantibodies are derived from or related to B cells of the fetal repertoire. Here we report that reactivity of plasma IgM against sulfatide was elevated in twelve MS patients compared with twelve normal subjects. This result implies that anti-sulfatide antibodies are disease-related. A total of sixteen human B lymphocyte clones producing anti-sulfatide autoantibodies were isolated from MS patients, GBS patients and a human fetus. Seven of the clones were from three MS patients, four of the clones were from three GBS patients and five were from the spleen of a twenty-week human fetus. Sequences have been obtained for the heavy and light chain variable regions (VDJ and VJ regions) of all of the anti-sulfatide immunoglobulins. Seven of the sixteen antibodies used VH3 for the variable region gene of the heavy chain consistent with the rate of VH3 usage in randomly selected B cells. Somatic mutations were significantly more frequent in the patient antibodies than in the fetus and somatic mutations in CDR's (Complementarity Determining Region) were significantly more frequent than in framework regions. No significant difference was found between patients and fetus in length of VH CDRIII. However, it is reported that antibodies from randomly selected normal adult B cells have longer CDRIII lengths than those of the fetus (Sanz I, 1991 Journal of Immunology Sep 1;147(5):1720-9). Our results are consistent with derivation of the precursors of B cells producing these autoantibodies from B cells related to those of the fetal repertoire. These findings are consistent with a model in which quiescent B cells from clones produced early in development undergo proliferation in dysregulated disease states, accumulating somatic mutations and increasing in reactivity toward self-antigens. ^ Epitope mapping and molecular modeling were done to elucidate the relationships between antibody structure and binding characteristics. The autoantibodies were tested for binding activity to three different antigens: sulfatide, galactoceramide and ceramide. Molecular modeling suggests that antibodies with positive charge surrounded by or adjacent to hydrophobic groups in the binding pocket bind to the head of sulfatide via the sulfate group through electrostatic interactions. However, the antibodies with hydrophobic groups separated from positive charges appear to bind to the hydrophobic tail of sulfatide. This observation was supported by a study of the effect of NaCl concentration on antigen binding. The result suggested that electrostatic interactions played a major role in sulfate group binding and that hydrophobic interactions were of greater importance for binding to the ceramide group. Our three-dimensional structure data indicated that epitope specificity of these antibodies is more predictable at the level of tertiary than primary structure and suggested positive selection based on structure occurred in the. formation of those autoantibodies. ^

Stomach content of ringed seals (Pusa hispida) obtained from the Northeast Greenland area

The diet of ringed seals (Pusa hispida) from coastal and offshore areas of Northeast Greenland was determined by identifying, to the lowest taxonomic limit possible, all hard-part contents from the gastrointestinal tract of 51 seals sampled (2002-2004) in spring (April to June, N = 35) and autumn (September to October, N = 16). The autumn diet was characterized by high numbers of Parathemisto libellula, and the spring diet was comprised primarily of polar cod (Boreogadus saida), with few invertebrates consumed. The coastal seal diet samples had a diverse fish prey composition (during both the spring and autumn), whereas the open water seals had eaten mostly crustaceans with P. libellula being most abundant. The sample sizes from the various locations and seasons were not large enough to explore age-class effects on diet in addition. Similar to earlier studies, this study suggests that the ringed seal is a generalist that exploits prey based on availability, with a few key species dominating the diet in an area at least on a seasonal basis.

Smith K. M. - A texbook of plant virus diseases (New second edition) J. A. Churchill Ltd, Londres, Inglaterra

Fil: Pontis, Rafael E..

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas