INTERACTIONS OF THE COMPLEMENT SYSTEM WITH ENDOTOXIC LIPOPOLYSACCHARIDE : GENERATION OF A FACTOR CHEMOTACTIC FOR POLYMORPHONUCLEAR LEUKOCYTES

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation. Preheating serum, incubating at 0°C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species. The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000–30,000) and as such different from previously scribed C' system-derived chemotactic factors. These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components

Sporulation, bacterial cell envelopes, and the origin of life

Electron cryotomography (ECT) enables the 3D reconstruction of intact cells in a near-native state. Images produced by ECT have led to the proposal that an ancient sporulation-like event gave rise to the second membrane in diderm bacteria. Tomograms of sporulating monoderm and diderm bacterial cells show how sporulation can lead to the generation of diderm cells. Tomograms of Gram-negative and Gram-positive cell walls and purified sacculi suggest that they are more closely related than previously thought and support the hypothesis that they share a common origin. Mapping the distribution of cell envelope architectures onto a recent phylogenetic tree of life indicates that the diderm cell plan, and therefore the sporulation-like event that gave rise to it, must be very ancient. One explanation for this model is that during the cataclysmic transitions of the early Earth, cellular evolution may have gone through a bottleneck in which only spores survived, which implies that the last bacterial common ancestor was a spore

Cost of hospital management of Clostridium difficile infection in United States - a meta-analysis and modelling study

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. Methods: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. Results: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90$ 39,886, $44,765) and$ 21,448 (90 % CI: $21,152,$ 21,744) in 2015 US dollars. Hospital-onset CDIattributable cost per case was $34,157 (90$ 33,134, $35,180), which was 1.5 times the cost of communityonset CDI ($ 20,095 [ 90 % CI: $4991,$ 35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range:$ 1.9-$ 7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. Conclusions: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.Sanofi PasteurSCI(E)[email protected]

Separation of a serum-derived tumoricidal factor from a helper factor for plaque-forming cells

C3H/HeN mice administered BCG followed by lipopolysaccharide 14 days later released into their serum a cytotoxic factor for tumor cells and a factor that restored the anti-SRBC plaque-forming cell response of nude mouse spleen cells (helper activity). Gel filtration of serum containing the cytotoxic and the helper activities indicated that both factors exhibited an apparent m.w. of 125,000 to 150,000. The helper activity was also found at lower m.w. (60,000 and 13,000) suggesting the possibility that this factor existed in aggregated forms. Gel filtration of ammonium sulfate (40 to 60% saturation) precipitated serum in a high ionic strength buffer (1.6 M NaCl) resulted in shifts in the apparent m.w. of both factors. The cytotoxic factor now exhibited a m.w. of 55,000. The helper activity eluted with an apparent m.w. of 13,000, and thus was clearly separated from the cytotoxic factor. The helper activity was further shown to co-elute with macrophage-derived lymphocyte activating factor (LAF). This as well as other data represent the first demonstration of in vivo produced LAF