Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. By positional cloning, we have identified the gene strongly associated with a form of degenerative ataxia (chromosome 16q22.1-linked ADCA) that clinically shows progressive pure cerebellar ataxia. Detailed examination by use of audiogram suggested that sensorineural hearing impairment may be associated with ataxia in our families. After restricting the candidate region in chromosome 16q22.1 by haplotype analysis, we found that all patients from 52 unrelated Japanese families harbor a heterozygous C-->T single-nucleotide substitution, 16 nt upstream of the putative translation initiation site of the gene for a hypothetical protein DKFZP434I216, which we have called "puratrophin-1" (Purkinje cell atrophy associated protein-1). The full-length puratrophin-1 mRNA had an open reading frame of 3,576 nt, predicted to contain important domains, including the spectrin repeat and the guanine-nucleotide exchange factor (GEF) for Rho GTPases, followed by the Dbl-homologous domain, which indicates the role of puratrophin-1 in intracellular signaling and actin dynamics at the Golgi apparatus. Puratrophin-1--normally expressed in a wide range of cells, including epithelial hair cells in the cochlea--was aggregated in Purkinje cells of the chromosome 16q22.1-linked ADCA brains. Consistent with the protein prediction data of puratrophin-1, the Golgi-apparatus membrane protein and spectrin also formed aggregates in Purkinje cells. The present study highlights the importance of the 5' untranslated region (UTR) in identification of genes of human disease, suggests that a single-nucleotide substitution in the 5' UTR could be associated with protein aggregation, and indicates that the GEF protein is associated with cerebellar degeneration in humans.

Presented is the new kindred with autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 (16q-ADCA type III) associated with progressive hearing loss. By haplotype analysis, the critical interval was slightly narrowed to three megabase regions between GATA01 and D16S3095. Neuropathologic study of 16q-ADCA type III demonstrated characteristic shrinkage of Purkinje cell bodies surrounded by synaptophysin-immunoreactive amorphous material containing calbindin- and ubiquitin-positive granules.

Cattle are an important reservoir of Shiga toxin-producingEscherichia coli (STEC) O26, O111, and O157. The fate of these pathogens in bovine feces at 5, 15, and 25°C was examined. The feces of a cow naturally infected with STEC O26:H11 and two STEC-free cows were studied. STEC O26, O111, and O157 were inoculated into bovine feces at 101, 103, and 105 CFU/g. All three pathogens survived at 5 and 25°C for 1 to 4 weeks and at 15°C for 1 to 8 weeks when inoculated at the low concentration. On samples inoculated with the middle and high concentrations, O26, O111, and O157 survived at 25°C for 3 to 12 weeks, at 15°C for 1 to 18 weeks, and at 5°C for 2 to 14 weeks, respectively. Therefore, these pathogens can survive in feces for a long time, especially at 15°C. The surprising long-term survival of STEC O26, O111, and O157 in bovine feces shows that such feces are a potential vehicle for transmitting not only O157 but also O26 and O111 to cattle, food, and the environment. Appropriate handling of bovine feces is emphasized.

A total of 1,835 Yersinia spp. were isolated from 925 (60.5%) of 1,530 wild mice and from 139 (79.9%) of 174 moles living in mountainous areas of eastern Shimane Prefecture, Japan. The Yersinia spp. included 1,106 Yersinia enterocolitica, 26 Y. enterocolitica-like, 176 Yersinia mollaretii, 149 Yersinia frederiksenii, 70 Yersinia intermedia, 231 Yersinia kristensenii, 5 Yersinia aldovae, and 72 Yersinia pseudotuberculosis. Human pathogenic Y. enterocolitica was not isolated. Y. pseudotuberculosis was divided into 10 virulent 40-to 50-MDa plasmid-positive (P+) strains (serotypes lb, 4b, and untypeable) and 62 plasmid-negative (P-) strains (serotypes lb, 2b, 2c, 4a, 5a, 5b, 6, 7, and untypeable). P+ strains of serotypes lb (two strains), 4b (seven strains), and untypeable (one strain) were isolated from nine Apodemus speciosus and one Apodemus argenteus. The isolates of Yersinia spp. were more frequently detected in newborn mice and during the breeding season. The P+ Y. pseudotuberculosis strains were recovered at less than 104 cells per g of the cecal contents. Thus, the prevalence of Yersinia spp. in small wild animals depends on the newborn animals born during the cold months, and wild mice in mountainous areas are important reservoirs of Y. pseudotuberculosis.

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