We explored the function of the human DEAD-box Y RNA helicase DBY (DDX3Y) gene located in the (AZFa) region on the human Y chromosome (Yq11.21). Deletion of this Y interval is known to be a major cause for the occurrence of a severe testicular pathology, the Sertoli-cell-only (SCO) syndrome. DBY has a structural homologue on the short arm of the X chromosome DBX (DDX3X) (Xp11.4). We found widespread transcription of both genes in each tissue analyzed, although predominantly in testis tissue. However, translation of DBY was detected only in the male germ line, whereas DBX protein was expressed in all tissues analyzed. In testis tissue sections, DBY protein was found predominantly in spermatogonia, whereas DBX protein was expressed after meiosis in spermatids. We conclude that although both RNA helicases are structurally very similar, they have diverged functionally to fulfill different roles in the RNA metabolism of human spermatogenesis, and that deletion of the DBY gene is the most likely cause of the severe testicular pathology observed in men with AZFa deletions.

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Whipple's disease is a rare chronic illness associated with an unculturable bacterium that is constantly present in affected tissues. This bacterium was previously characterized at the molecular level by PCR and sequencing of the 16s rRNA gene. On the basis of 1,321 nucleotides of the sequence of its gene coding for 16s rRNA (16s rDNA), a phylogenetic relationship to the actinomycetes was established. In this study, we determined an almost complete 16s rDNA sequence (1,495 nucleotides), the 16s-235 ribosomal intergenic spacer sequence, and 200 nucleotides of the 23s rRNA gene. The 16s rDNA sequence was compared with the large number of actinomycete sequences that have been added to the database since the original study. Phylogenetic analysis revealed a branching position as the deepest branch of the cluster comprising the actinomycetes with group B peptidoglycan between this group and the family Cellulomonadaceae. This provides additional information on the phylogenetic position of this bacterium and some clues as to its characteristics. The spacer region between the 16s and 23s rRNA genes is 294 nucleotides long and does not contain tRNA genes. As has been shown in other instances, the increased variability of the ribosomal intergenic spacer compared with the 16s rRNA gene makes it a potential target for use in the differentiation of strains of the bacterium associated with Whipple's disease.Whipple's disease is a rare chronic illness with intestinal and extraintestinal manifestations. A constant feature of the disease is the appearance of periodic acid-Schiff stain-positive cellular inclusions detected by histology. These periodic acidSchiff stain-positive inclusions contain bacteria visible by electron microscopy that are approximately 0.2 pm wide by 1.5 to 2.5 p,m long and have a typical trilaminar appearance of the cell wall (4). Numerous attempts to culture these bacteria on artificial media or in cell culture have failed or have yielded contaminants (3). The bacterium associated with Whipple's disease (Whipple's disease bacterium) was characterized at the molecular level by PCR and universal bacterial primers for the 16s rRNA gene; the resulting PCR products were sequenced (36,48). In a first investigation, less than 50% (645 nucleotide positions) of the bacterial 16s rRNA gene was sequenced and a relationship to the actinomycetes was established, with the closest relative reported to be Rhodococcus equi (48). Later, approximately 85% of the 16s rRNA gene was sequenced (36). Analysis of this sequence comprising 1,321 bp confirmed a phylogenetic relationship to the actinomycetes (36). The closest phylogenetic relatives within the order Actinomycetales were members of a group designated the "actinobacteria" comprising representatives of the genera Actinomyces, Rothia, Arthrobacter, Micrococcus, Terrabacter, and Dewnatophilus for which sequence data had been previously determined and rnade available via the public databases and the Ribosomal Database Project (25,36). On the basis of the novelty of the * Corr...

Whipple's disease is an infectious disorder with intestinal and extra-intestinal manifestations. We reinvestigated the intestinal histology in a series of 48 patients (10 females, 38 males; mean age 56.5 years, standard deviation of the mean +/- 11.2 years). A total of 126 biopsy samples, obtained prior to, during, and after therapy, were evaluated by light microscopy. In 43 patients (90%), histology was consistent with common descriptions, while it was uncommon in 3 patients (6%), and non-diagnostic in 2 patients (4%). During treatment, several alterations occurred. Apart from a continuous decrease in PAS-positive macrophages, the pattern of mucosal infiltration changed from diffuse to patchy. Moreover, the cytological aspects of PAS-positive macrophages changed substantially, and this change was used to propose four different subtypes. Initially, subtype 1 macrophages predominated (74%), but showed a gradual decrease within a few months of therapy. After 15 months, subtype 3 and subtype 4 macrophages predominated (< 80%). In 7 of 9 patients followed over long periods some subtype 3 or subtype 4 macrophages persisted. It is concluded that at diagnosis and during treatment the intestinal histology of Whipple's disease is heterogeneous. A few PAS-positive macrophages commonly persist at long-term follow-up. This and other features suggest the presence of a persistent immune defect.

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Whipple's disease is not quite as rare as commonly assumed. There is no obvious geographic predominance. During the past three decades, the demography of WD patients has changed.

Whipple’s disease is a systemic disorder in which a gram-positive rod-shaped bacterium is constantly present in infected tissues. After numerous unsuccessful attempts to culture this bacterium, it was eventually characterized by 16S rRNA gene analysis to be a member of the actinomycetes. The name Tropheryma whippelii was proposed. Until now, the bacterium has only been found in infected human tissues, but there is no evidence for human-to-human transmission. Here we report the detection of DNA specific for the Whipple’s disease bacterium in 25 of 38 wastewater samples from five different sewage treatment plants in the area of Heidelberg, Germany. These findings provide the first evidence that T. whippeliioccurs in the environment, within a polymicrobial community. This is in accordance with the phylogenetic relationship of this bacterium as well as with known epidemiological aspects of Whipple’s disease. Our data argue for an environmental source for infection with the Whipple’s disease bacterium.

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