Management of chronic viral hepatitis in HIV-infected patients: Spanish Consensus Conference. October 2000

Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed.     

Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNgamma production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.     

Immunohistochemical classification of non-BRCA1/2 tumors identifies different groups that demonstrate the heterogeneity of BRCAX families.

Around 25% of hereditary breast and ovarian cancer families have mutations in the BRCA1 and BRCA2 genes. The search for other genes has until now failed, probably because there is not one single BRCAX gene, but rather various genes that may each be responsible for a small number of breast cancer families and/or may interact according to a polygenic model. We have studied 50 tumors from probands belonging to non-BRCA1/2 breast cancer families (BRCAX), using 25 immunohistochemical markers. The objective was to classify these tumors and confirm that they are heterogeneous. Unsupervised cluster analysis showed the existence of the following two main groups of tumors: high-grade and estrogen receptor (ER)-negative tumors (50%), and low-grade and ER-positive tumors (50%). In addition we identified five subgroups, three among the high-grade and two among the low-grade groups; one overexpressing HER-2 (18%); one with a basal-like phenotype (14%); one with a normal breast-like phenotype (18%); a luminal A subgroup (36%), and a luminal B subgroup (14%). Hypermethylation of the BRCA1 gene was observed in 42% of the cases, spread across all five subgroups, but only 37% of those had loss of heterozygosity as well. These latter cases were all clustered in the high-grade group and the majority of them in the basal-like subgroup. Our results show that familial non-BRCA1/2 tumors are heterogeneous and suggest a polygenic model for explaining the majority of BRCAX families. In addition we have defined a subset of them that have somatic inactivation of the BRCA1 gene.     

Isolation and identification of pathogenic Acanthamoeba strains in Tenerife, Canary Islands, Spain from water sources

A comprehensive survey to document the presence of free-living amoebae of the genus Acanthamoeba was conducted in tap water and sea water sources related to human environments in Tenerife, Canary Islands, Spain. Acanthamoeba identification was based on the morphology of cyst and trophozoite forms and PCR amplification with a genus-specific primer pair. The pathogenic potential of Acanthamoeba isolates was characterized by temperature and osmotolerance assays and PCR reactions with two primer pairs related to Acanthamoeba pathogenesis. The results demonstrate the presence of potentially pathogenic strains in both sources. Thus, some of the amoebae in these aquatic habitats can act as opportunistic pathogens, could play a role in the diseases of aquatic organisms, and may present a risk to human health.     

Significantly reduced expression of the proteoglycan decorin in Alzheimer''s disease fibroblasts

Aims—To investigate whether proteoglycan synthesis is altered in skin fibroblasts in patients with Alzheimer's disease compared with normal subjects.