17 research outputs found

    Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

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    Background: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified

    Subcellular Recruitment of Fibrillarin to Nucleoplasmic Proteasomes: Implications for Processing of a Nucleolar Autoantigen

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    A prerequisite for proteins to interact in a cell is that they are present in the same intracellular compartment. Although it is generally accepted that proteasomes occur in both, the cytoplasm and the nucleus, research has been focusing on cytoplasmic protein breakdown and antigen processing, respectively. Thus, little is known on the functional organization of the proteasome in the nucleus. Here we report that within the nucleus 20S and 26S proteasomes occur throughout the nucleoplasm and partially colocalize with splicing factor–containing speckles. Because proteasomes are absent from the nucleolus, a recruitment system was used to analyze the molecular fate of nucleolar protein fibrillarin: Subtoxic concentrations of mercuric chloride (HgCl(2)) induce subcellular redistribution of fibrillarin and substantial colocalization (33%) with nucleoplasmic proteasomes in different cell lines and in primary cells isolated from mercury-treated mice. Accumulation of fibrillarin and fibrillarin-ubiquitin conjugates in lactacystin-treated cells suggests that proteasome-dependent processing of this autoantigen occurs upon mercury induction. The latter observation might constitute the cell biological basis of autoimmune responses that specifically target fibrillarin in mercury-mouse models and scleroderma
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