Toxicity of pneumolysin to pulmonary alveolar epithelial cells.

Mortality during the first several days of pneumococcal pneumonia has not decreased appreciably over the past 30 years, despite the widespread use of antibiotics. Disruption of the alveolar epithelial barrier is likely an initial step in the pathogenesis of pneumococcal pneumonia. We report that soluble factors from Streptococcus pneumoniae can directly injure isolated rat alveolar epithelial cells. Using biochemical and immunological techniques, we identified pneumolysin as a major soluble S. pneumoniae toxin for alveolar epithelial cells. Alveolar epithelial cells at 24 or 72 h after isolation were equally sensitive to injury by purified pneumolysin. Purified pneumolysin substantially increased alveolar permeability in an isolated perfused rat lung model. Electron microscopy revealed that instilled pneumolysin caused widespread lung injury, primarily to type I alveolar epithelial cells. Pneumolysin toxicity to alveolar epithelial cells may be important in the pathogenesis of acute lung injury during pneumococcal pneumonia and may facilitate pneumococcal bacteremia.     

Chromosome 13q neocentromeres: molecular cytogenetic characterization of three additional cases and clinical spectrum

We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions.     

Opsonin-independent phagocytosis of surface-adherent bacteria by human alveolar macrophages

Opsonin-independent mechanisms of phagocytosis may be important in host defense of certain body sites such as the lung. In this study, one such mechanism, "surface phagocytosis," was investigated by measuring the uptake of unopsonized [3H]-labeled Staphylococcus aureus and Pseudomonas aeruginosa adherent to a plastic surface by human alveolar macrophages (AM) and peripheral blood polymorphonuclear leukocytes (PMN). Efficient uptake of unopsonized bacteria by both cell types was observed. Electron microscopic studies suggested that the manner in which these cell types encounter adherent bacteria is different. While AM appear to gather in organisms at their periphery as they spread out upon the underlying substrate, PMN seem to sweep bacteria up as they move along the plastic surface. Bacterial killing determined by a fluorochrome microassay was decreased by AM compared to PMN. Although the precise mechanism whereby phagocytes recognize unopsonized bacteria adherent to a surface remains to be determined, this aspect of phagocytic cell function may prove to have clinical relevance.     

Platelet interaction with bacteria. V. Ultrastructure of congenital afibrinogenemic platelets.

Platelets from a patient with congenital afibrinogenemia (CA) were tested in their native plasma for reactivity in vitro to Staphylococcus aureus 502A. Previous studies of the interactions between normal human platelets and this organism have shown rapid irreversible aggregation responses in which the bacteria were regularly trapped between aggregating platelets. Engulfment of microbes by single normal platelets in a process akin to phagocytosis was a very rare occurrence. In contrast, CA platelets showed a delayed aggregation response to contact with this microorganism. The CA platelets were also much more sensitive to the concentration of bacteria than were normal platelets. Electron microscopy showed that individual CA platelets often engulfed the stimulatory organism rather than participating in aggregation. Postfixation staining with a colloidal tracer, lanthanum nitrate, indicated that the bacteria were sequestered in the open canalicular system of the CA platelets in a manner analogous to that previously observed with latex particles. Restoration of normal levels of human fibrinogen to the CA platelet-rich plasma corrected the delay in aggregation but did not eliminate the frequent engulfment of bacteria by the CA platelets. These findings indicate that fibrinogen is an important, although not essential, cofactor in the response of human platelets to contact with this common bacterial pathogen.     

Inverse association between smoking and idiopathic Parkinson's disease

An evaluation is made of the effect of smoking during the period of life between 20 and 50 years of age and idiopathic Parkinson's disease in a case-control study carried out in Navarra. An inverse association is observed: for the number of smokers (OR = 0.66, CI 90% 0.41-1.05); for the number of years smoking (OR =0.22, CI 90% 0.05-0.97); and for the quantity of cigarettes smoked (z = 2.2298, p = 0.02). Likewise, a dose-response relationship exists between the number of cigarettes consumed and the risk of Parkinson's disease (p = 0.01). The same effect is maintained on analysing the data by matching 1:1 (OR = 0.59, CI 90% 0.31-1.10). All of this contributes to giving consistency to the protective effect of smoking against idiopathic Parkinson's disease. The anti-oxidant status, measured by means of different parameters in peripheral blood, is lower in the cases than in the tests for reduced glutathione (GSH) (p = 0.001) and is an independent variable with respect to smoking.