Thesis--Copenhagen. / Bibliography: p. [191]-195.

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 186-199).

Thesis (doctoral)--University of Uppsala, 1981. / Includes bibliographical references (p. 15-17).

Proefschrift--Utrecht. / Bibliography: p. 259-262.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 142-146).

Thesis (doctoral)--Lund University, 1997.

Inaugural dissertation.--Universität Greifswald, 1899.

Thesis (M.D.)--Boston University

Repeated administration of ochratoxin A (OTA) caused renal morphological dose-related changes, that were associated with proximal tubular and glomerular damage the latter showing oedema and prominent PAS staining suggestive of glomerular basement membrane thickening. On the other hand, the combined administration of repeated doses of OTA and aflatoxin B[1] (2. 5 mg and 100 ug per kg, respectively), appeared to have a synergistic effect, characterized by severe disruption of proximal tubules and general morphological derrangement of the glomerulus, involving intense and faint staining nuclei (suggestive of cell necrosis) and cytoplasmic vacuolation, which was not seen with either toxin alone. When clinical biochemical parameters were measured after repeated administration of a low dose of OTA, enzymuria, glucosuria, polyuria and proteinuria were observed, with glucose and alkaline phosphatase as the most sensitive parameters. Metabolic studies performed in vitro showed that isolated pig and rat glomeruli incorporate different amino acids linearly for several hours at different rates and perform oxidative metabolism of glucose and fatty acids to CO[2] also linearly. For pig glomeruli the order of amino acid incorporation was LEU >> PRO = HIS > LYS > GLY and for rat glomeruli it was TRP >> PHE > TYR = LEU > PRO > HIS. The same amino acids were incorporated in a similar way in rat tubules, but the incorporation rate is 10-fold lower. When de novo synthesis of protein by pig glomeruli exposed to different chemicals was assessed, using proline (PRO) as the precursor, adriamycin (ADR) and ethacrynic acid (ETA) inhibited protein synthesis more than 2-bromoethanamine (BEA) and streptomycin (STR), and much more than puromycin aminonucleoside (PAN). When isolated rat glomeruli were exposed to low concentrations of OTA, there was a generalized inhibition on de novo synthesis of protein from the six amino acids tested and the aromatic amino acids (TRP, TYR and PHE) were more sensitive to OTA effect than PRO. Low concentrations of OTA (10 - 100 uM) enhanced glomerular and tubular glucose metabolism to CO[2] and only high concentrations of the mycotoxin (1000 uM) caused significant inhibition of glomerular and proximal tubular linolenic acid metabolism.

Urine contains exosomes originating from the circulation and all cells lining the urinary tract. Exosomes are a route of inter-cellular communication along the nephron potentially able to transfer of protein and/or RNA. It is not known whether this is a regulated process analogous to other cell-to-cell signalling systems. The aims of this study were to develop nanoparticle tracking analysis (NTA) as a technique to quantify exosomes in urine. Secondly, the hormonal regulation of exosome uptake in vitro and in vivo was investigated. Thirdly, exosome excretion in a central diabetes insipidus (DI) patient and a patient group after radiocontrast exposure was measured to investigate exosome excretion along the kidney in injury. Using the fluorescent capabilities of NTA, urinary exosomes were quantified in urine samples. NTA was able to detect changes in aquaporin 2 levels in vitro and in vivo. Storage conditions for human urinary exosomes were also optimised using NTA. A kidney cortical collecting duct cell line (CCDs) was used to model regulation of exosome uptake in vitro. CCDs were stimulated with desmopressin, a vasopressin analogue, and uptake of fluorescently-loaded or microRNA-loaded exosomes was measured. Desmopressin stimulated exosome uptake into collecting duct cells via V2 receptor stimulation. Intra-cellular uptake of exosomes was confirmed by microRNA specific mRNA down-regulation. Mechanistically, exosome uptake in response to desmopressin required cyclic AMP production, was mediated by clathrin-dependent endocytosis and was selective for exosomes from kidney tubular cells. In mice, fluorescently-loaded exosomes were systemically injected before and after administration of the V2 antagonist, tolvaptan, and urinary exosome excretion was measured. Basally, 2.5% of injected exosomes were recovered in urine; tolvaptan treatment resulted in a 5-fold increase. By combining antibodies to nephron segment-specific proteins with NTA we measured human urinary exosome excretion in central diabetes insipidus (DI) and after radiocontrast exposure (n=37). In DI, desmopressin reduced the excretion of exosomes derived from upstream glomerular and proximal tubule cells. In patients exposed to radiocontrast, urinary exosomes from the glomerulus were positively correlated with the tubular injury markers KIM- 1 and NGAL. These findings therefore show that tubular exosome uptake is a specific, hormonally regulated process that is reduced with injury. Physiologically, exosomes are a mechanism of inter-cellular communication; therapeutically, exosomes represent a novel vehicle by which RNA therapy could be targeted for the treatment of kidney disease.