Susceptibility of Clostridium septicum to 23 Antimicrobial Agents

The in vitro susceptibility of Clostridium septicum was studied with a microtiter broth dilution method. Several antimicrobial agents demonstrated consistently good activity against the organism.     

Isolation and characterization of the cytoplasmic and outer membranes of the Legionnaires'' disease bacterium (Legionella pneumophila)

Legionella pneumophila, the etiologic agent of Legionnaires' disease, is phagocytized in an unusual way and multiplies in human mononuclear phagocytes in a novel phagosome. As a first step toward understanding these L. pneumophila-phagocyte interactions, we have studied the envelope of L. pneumophila Philadelphia 1 strain. We isolated cell envelopes by treating whole bacterial cells with lysozyme and EDTA to convert them to spheroplasts, then lysing the spheroplasts osmotically or sonically. We resolved the cell envelopes into two membrane fractions by isopycnic centrifugation. We localized NADH oxidase to the fraction of buoyant density 1.145, which we designated cytoplasmic membrane, and lipopolysaccharide (LPS) to the fraction of density 1.222, which we designated outer membrane. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the L. pneumophila outer membrane contains a single major protein species migrating at 28,000 mol wt; this is the major protein of the bacterium. The cytoplasmic membrane also contains a single major protein species migrating at 65,000 mol wt. Surface iodination of the bacteria and agglutination and immunofluorescence studies with rabbit antibody produced against the purified major outer membrane protein (MOMP) revealed that this protein is exposed at the cell surface. We isolated LPS from L. pneumophila membranes by SDS-EDTA treatment. The pattern obtained by subjecting the LPS to SDS-PAGE and staining the gel with silver nitrate suggests that L. pneumophila LPS might be atypical. We studied patient serologic responses to cell envelope components of L. pneumophila Philadelphia 1, a serogroup 1 organism. Sera from patients with evidence of infection with serogroup 1 L. pneumophila contained large amounts of antibody to this strain. Few of these antibodies recognized the MOMP of L. pneumophila. In contrast, greater than 98% of these antibodies were directed against the LPS. This indicates that LPS is the dominant serogroup antigen and the major antigen responsible for the reactivity of patient sera in the indirect fluorescent antibody assay, currently the principal diagnostic assay for Legionella infection.     

Do gender, education, and income modify the effect of air pollution gases on cardiac disease?

OBJECTIVE: We sought to determine whether gender, education, and income influence the susceptibility to ambient air pollution. METHODS: We determined the association between daily cardiac hospitalizations and daily concentrations of gaseous air pollutants in 10 large Canadian cities using time-series analyses adjusted for day-of-the week, temperature, barometric pressure, relative humidity. RESULTS: Percentage increases in hospitalization associated with an increase in air pollution equivalent to its mean value were statistically significant for ozone, carbon monoxide and nitrogen dioxide individually (P < 0.05) and the combined pollutant effect was 8.5% (95% confidence interval: 1.8, 14.6). The air pollution-cardiac disease association was not significantly influenced by gender or community level of education or income. CONCLUSION: Short-term changes in air pollution may adversely affect cardiac disease but gender, and community education and income do not accurately identify those with increased susceptibility.     

The cost of Medicaid annuities

Medicaid annuities are annuities that long-term care recipients use to shelter assets, thereby qualifying them early for Medicaid eligibility. As such, these annuities have the potential to increase Medicaid costs. This study estimates the cost of annuities to the Medicaid program. From a sample of Medicaid applications in five states, we found the rate at which annuities were used and simulated their cost to Medicaid. We estimated that in 2004, Medicaid annuities cost Medicaid about 197 million dollars, which represented a small proportion of Medicaid's almost 50 billion dollars cost for nursing home care.     

Treatment of rheumatoid arthritis with IL-1 inhibitors

Summary Extensive evidence from both in vivo and in vitro experiments indicate that IL-1, a prototypic proinflammatory cytokine, is involved in the mechanisms that lead to progressive joint destruction in RA. IL-1Ra, a member of the IL-1 family, binds IL-1 receptors but does not induce any cellular responses. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus, acts as an endogenous anti-inflammatory mediator. However, the results of several studies suggest that a relatively deficient production in IL- 1Ra as compared to that of IL-1 in RA synovium may pre-dispose to the perpetuation of chronic inflammation. Systemic administration of IL-1Ra, or local delivery into the joints by gene therapy, in different experimental animal models of arthritis attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of rheumatoid patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Encouraging results also have been reported in both in vitro and in vivo experimental animal models of arthritis through using other strategies designed to block the effects of IL-1 at the level of production, prevent the binding of IL-1 to its cell surface receptors, or interfere with the effects of IL-1 at the post-receptor level.     

IL-36R ligands are potent regulators of dendritic and T cells

IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) are members of the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5) acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine bone marrow-derived dendritic cells (BMDCs) and CD4(+) T lymphocytes constitutively express IL-36R and respond to IL-36α, IL-36β, and IL-36γ. IL-36 induced the production of proinflammatory cytokines, including IL-12, IL-1β, IL-6, TNF-α, and IL-23 by BMDCs with a more potent stimulatory effect than that of other IL-1 cytokines. In addition, IL-36β enhanced the expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the production of IFN-γ, IL-4, and IL-17 by CD4(+) T cells and cultured splenocytes. These stimulatory effects were antagonized by IL-36Ra when used in 100- to 1000-fold molar excess. The immunization of mice with IL-36β significantly and specifically promoted Th1 responses. Our data thus indicate a critical role of IL-36R ligands in the interface between innate and adaptive immunity, leading to the stimulation of T helper responses.