We previously found that sustained ERK activation contributes to toxicity elicited by the parkinsonian neurotoxin 6-hydroxydopamine. In addition, substantia nigra neurons from patients with incidental Lewy body disease, Parkinson's disease (PD), and diffuse Lewy body dementia (DLB) display abnormal phospho-ERK accumulations in the form of discrete cytoplasmic granules. In this study, we investigated the subcellular localization of phospho-ERK immunoreactive granules using double label confocal microscopy and immuno-electron microscopy. A small percentage of phospho-ERK granules co-localized with the early endosome marker Rab5, but not with cathepsin D, 20S proteasome β-subunit, or cytochrome P450 reductase. Phospho-ERK immunoreactivity was often associated with mitochondrial proteins (MnSOD, 60 kDa and 110 kDa mitochondrial antigens), and some vesicular-appearing phospho-ERK granules appeared to envelop enlarged mitochondria by confocal laser scanning microscopy. Ultrastructural immuno-gold studies revealed phospho-ERK labeling in mitochondria and in association with bundles of ~10 nm fibrils. Heavily labeled mitochondria were observed within autophagosomes. As mitochondrial pathology may play a pivotal role in Parkinson's and other related neurodegenerative diseases, these studies suggest a potential interaction between dysfunctional mitochondria, autophagy, and ERK signaling pathways.

Fungal peritonitis is a rare complication in patients on continuous ambulatory peritoneal dialysis. We report five recent cases and their management. The fungi isolated were Candida albicans, C. parapsilosis, Exophiala jeanselmei, Drechslera spicifera, and a Fusarium species. Chemotherapy was attempted with various regimens including oral ketoconazole, intravenous or intraperitoneal amphotericin B, and oral flucytosine. Pharmacokinetic studies were done in two patients receiving treatment with one of these drugs. Three patients were cured of their fungal infection. Three patients whose Tenckhoff catheters were left in situ died, whereas two patients whose catheters were removed survived. Our experience suggests that removal of the peritoneal catheter should be considered once the diagnosis of fungal peritonitis is established.

No abstract

No abstract