Subretinal lesions in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurologic disorder. A 9-year-old boy was seen who had progressive neurocognitive decline, myoclonic jerking of the extremities, and an abnormal result of an electroencephalogram (EEG). Ophthalmoscopic examination revealed multifocal subretinal lesions. The diagnosis of SSPE was made on the basis of the clinical examination and elevated serum and spinal fluid measles titer. We describe subretinal lesions in a patient with SSPE.

Inhibition of macrophage phagocytosis by Pseudomonas aeruginosa rhamnolipids in vitro and in vivo.

Patients with cystic fibrosis often have chronic and ultimately lethal pulmonary infections with Pseudomonas aeruginosa. In order to understand why these bacteria resist pulmonary clearance, we have investigated the interaction of P. aeruginosa and phagocytic cells. In an earlier study we reported that sub-lytic concentrations of two glycolipids produced by P. aeruginosa (the mono- and dirhamnolipids) caused structural changes in human monocyte-derived macrophages, and at lower concentrations inhibited the phagocytosis of Staphylococcus epidermidis by these cells. In the present study we demonstrate that rhamnolipids also inhibit the in vitro phagocytosis of both P. aeruginosa and Saccharomyces cerevisiae by thioglycollate-elicited mouse peritoneal macrophages. Using lucifer yellow to label the lysosomal compartments of macrophages, we determined that rhamnolipids interfere with the internalization of attached particles and reduce the level of phagosome-lysosome fusion of internalized targets within macrophages. We also demonstrate that physiologically relevant concentrations of rhamnolipids injected intratracheally into rat lungs inhibited the response of alveolar macrophages to a challenge of zymosan particles in vivo. These studies further demonstrate the profound inhibitory effects of P. aeruginosa rhamnolipids on macrophage function and are consistent with our hypothesis that the in situ production of these rhamnolipids directly contributes to the persistence of this pathogen in cystic fibrosis patient lungs.

Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Pseudomonas aeruginosa rhamnolipids on human monocyte-derived macrophages.

Pseudomonas aeruginosa, a major opportunistic gram-negative pathogen, produces and secretes two heat-stable hemolytic glycolipids, a monorhamnolipid and a dirhamnolipid. In this paper a simplified method for the isolation of these rhamnolipids is described. The effect of these two rhamnolipids, both together and individually, on the viability and structural morphology of human monocyte-derived macrophages (MDMs) was examined. These cells were found to be very susceptible to the cytolytic activity of the rhamnolipids, particularly the dirhamnolipid. The monorhamnolipid, although not as cytolytic as the dirhamnolipid, caused extensive blebbing of the MDM plasma membrane. Comparison studies with several detergents confirmed the different yet distinct detergent-like activity of each rhamnolipid form. At sublethal doses, the rhamnolipids produced marked cellular distortions of the MDMs and inhibited the ability of these cells to bind and/or ingest preopsonized bacteria. The potential mechanism of action of these rhamnolipids on the MDM membranes is discussed, as well as the possible significance of these extracellular bacterial glycolipids as a virulence factor in the pathogenesis of P. aeruginosa.

Demonstration of differential immunohistochemical localization of the neuron-specific enolase antigen in rat pinealocytes.

A refined method for the immunohistological demonstration of neuron-specific enolase (NSE) on 1- to 2-micron Epon-812 section gave characteristic staining of cerebral and cerebellar neurons. This method has made it possible to obtain a more detailed characterization of the heterogeneity of rat pinealocytes in the superficial portion of the rat pineal complex. Thirty adult male rats have been studied, five of which were used in a photometric analysis of the distribution of NSE. Pinealocytes stained either intensely or weakly for the NSE antigen and exhibited an uneven distribution within a given region. Further analysis of the gland revealed a distal to proximal decrease in stain intensity. It is suggested that the more strongly stained cells, being concentrated distally, are under sympathetic control.