"Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.

One thermophilic (strain IMO-1T) and two mesophilic (strains KIBI-1T and YMTK-2T) non-spore-forming, non-motile, Gram-negative, multicellular filamentous micro-organisms, which were previously isolated as members of the tentatively named class ‘Anaerolineae’ of the phylum Chloroflexi, were characterized. All isolates were strictly anaerobic micro-organisms. The length of the three filamentous isolates was greater than 100 μm and the width was 0.3–0.4 μm for strain IMO-1T, 0.4–0.5 μm for strain KIBI-1T and thinner than 0.2 μm for strain YMTK-2T. Strain IMO-1T could grow at pH 6.0–7.5 (optimum growth at pH 7.0). The optimal temperature for growth of strain IMO-1T was around 50 °C (growth occurred between 42 and 55 °C). Growth of the mesophilic strains KIBI-1T and YMTK-2T occurred at pH 6.0–7.2 with optimal growth at pH 7.0. Both of the mesophilic strains were able to grow in a temperature range of 25–50 °C with optimal growth at around 37 °C. Yeast extract was required for growth of all three strains. All the strains could grow with a number of carbohydrates in the presence of yeast extract. The G+C contents of the DNA of strains IMO-1T, KIBI-1T and YMTK-2T were respectively 53.3, 59.5 and 48.2 mol%. Major fatty acids for thermophilic strain IMO-1T were anteiso-C17 : 0, iso-C15 : 0, C16 : 0 and anteiso-C15 : 0, whereas those for mesophilic strains KIBI-1T and YMTK-2T were branched C14 : 0, iso-C15 : 0, C16 : 0 and branched C17 : 0, and branched C17 : 0, C16 : 0, C14 : 0 and C17 : 0, respectively. Detailed phylogenetic analyses based on their 16S rRNA gene sequences indicated that the isolates belong to the class-level taxon ‘Anaerolineae’ of the bacterial phylum Chloroflexi, which for a long time had been considered as a typical uncultured clone cluster. Their morphological, physiological, chemotaxonomic and genetic traits strongly support the conclusion that these strains should be described as three novel independent taxa in the phylum Chloroflexi. Here, Anaerolinea thermolimosa sp. nov. (type strain IMO-1T=JCM 12577T=DSM 16554T), Levilinea saccharolytica gen. nov., sp. nov. (type strain KIBI-1T=JCM 12578T=DSM 16555T) and Leptolinea tardivitalis gen. nov., sp. nov. (type strain YMTK-2T=JCM 12579T=DSM 16556T) are proposed. In addition, we formally propose to subdivide the tentative class-level taxon ‘Anaerolineae’ into Anaerolineae classis nov. and Caldilineae classis nov. We also propose the subordinate taxa Anaerolineales ord. nov., Caldilineales ord. nov., Anaerolineaceae fam. nov. and Caldilineaceae fam. nov.

The amyloid beta-protein (Abeta) ending at 42 plays a pivotal role in Alzheimer's disease (AD). We have reported previously that intracellular Abeta42 is associated with neuronal apoptosis in vitro and in vivo. Here, we show that intracellular Abeta42 directly activated the p53 promoter, resulting in p53-dependent apoptosis, and that intracellular Abeta40 had a similar but lesser effect. Moreover, oxidative DNA damage induced nuclear localization of Abeta42 with p53 mRNA elevation in guinea-pig primary neurons. Also, p53 expression was elevated in brain of sporadic AD and transgenic mice carrying mutant familial AD genes. Remarkably, accumulation of both Abeta42 and p53 was found in some degenerating-shape neurons in both transgenic mice and human AD cases. Thus, the intracellular Abeta42/p53 pathway may be directly relevant to neuronal loss in AD. Although neurotoxicity of extracellular Abeta is well known and synaptic/mitochondrial dysfunction by intracellular Abeta42 has recently been suggested, intracellular Abeta42 may cause p53-dependent neuronal apoptosis through activation of the p53 promoter; thus demonstrating an alternative pathogenesis in AD.