Gamma-Interferon-Induced Nitric-Oxide Production Reduces Chlamydia-Trachomatis Infectivity in McCoy Cells

McCoy cells, murine-derived cells commonly used for propagation of chlamydiae, were found to be efficient producers of nitric oxide (NO) when primed with murine gamma interferon (IFN-gamma) and then exposed to the second signals provided by Escherichia coli lipopolysaccharide, human interleukin-1 alpha, murine tumor necrosis factor alpha, or Chlamydia trachomatis type H. Murine recombinant IFN-gamma over a range of 0 to 50 U/ml inhibited infectivity of C. trachomatis type H in a dose-dependent fashion in McCoy cells while simultaneously inducing NO production. Quantitation of infectious chlamydia progeny remaining in McCoy cells 48 or 72 h postinfection revealed that IFN-gamma-primed McCoy cells reduced chlamydial inclusion-forming units (expressed as units per milliliter) by 4 log10 units at higher IFN-gamma concentrations (50 U/ml) compared with control values. The magnitude of this antichlamydial effect was directly related to increased synthesis of NO, the production of which was IFN-gamma dose dependent. The antichlamydial effects of IFN-gamma were blocked in a dose-dependent manner by the addition of N-guanidino-monomethyl L-arginine (MLA), an inhibitor of nitric oxide synthesis. These results suggest that although IFN-gamma priming of McCoy cells is required for antichlamydial activity, nitric oxide is a necessary effector molecule involved in the mechanism(s) of IFN-gamma-induced inhibition of chlamydial proliferation in this murine cell line. The ability to block the potent antichlamydial effects of IFN-gamma by inhibition of a specific enzyme, nitric oxide synthase, may give insights into mechanisms by which IFN-gamma and perhaps other cytokines are able to control proliferation of chlamydiae and other intracellular pathogens

Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice

OBJECTIVE: Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells. DESIGN: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year. RESULTS: Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p \u3c 0.05 vs control) whereas expression of IFN-gamma and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3. CONCLUSIONS: Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice

Effects of climate variability and accelerated forest thinning on watershed-scale runoff in southwestern USA ponderosa pine forests

The recent mortality of up to 20% of forests and woodlands in the southwestern United States, along with declining stream flows and projected future water shortages, heightens the need to understand how management practices can enhance forest resilience and functioning under unprecedented scales of drought and wildfire. To address this challenge, a combination of mechanical thinning and fire treatments are planned for 238,000 hectares (588,000 acres) of ponderosa pine (Pinus ponderosa) forests across central Arizona, USA. Mechanical thinning can increase runoff at fine scales, as well as reduce fire risk and tree water stress during drought, but the effects of this practice have not been studied at scales commensurate with recent forest disturbances or under a highly variable climate. Modifying a historical runoff model, we constructed scenarios to estimate increases in runoff from thinning ponderosa pine at the landscape and watershed scales based on driving variables: pace, extent and intensity of forest treatments and variability in winter precipitation. We found that runoff on thinned forests was about 20% greater than unthinned forests, regardless of whether treatments occurred in a drought or pluvial period. The magnitude of this increase is similar to observed declines in snowpack for the region, suggesting that accelerated thinning may lessen runoff losses due to warming effects. Gains in runoff were temporary (six years after treatment) and modest when compared to mean annual runoff from the study watersheds (0–3%). Nonetheless gains observed during drought periods could play a role in augmenting river flows on a seasonal basis, improving conditions for water-dependent natural resources, as well as benefit water supplies for downstream communities. Results of this study and others suggest that accelerated forest thinning at large scales could improve the water balance and resilience of forests and sustain the ecosystem services they provide

Implementing automated surveillance for tracking Clostridium difficile infection at multiple healthcare facilities

Automated surveillance utilizing electronically available data has been found to be accurate and save time. An automated CDI surveillance algorithm was validated at four CDC Prevention Epicenters hospitals. Electronic surveillance was highly sensitive, specific, and showed good to excellent agreement for hospital-onset; community-onset, study facility associated; indeterminate; and recurrent CDI

Multicenter study of the impact of community-onset Clostridium difficile infection on surveillance for C. difficile infection

OBJECTIVE: To evaluate the influence of community-onset/healthcare facility-associated cases on Clostridium difficile infection (CDI) incidence and outbreak detection. DESIGN: Retrospective cohort. SETTING: Five acute-care healthcare facilities in the United States. METHODS: Positive stool C. difficile toxin assays from July 2000 through June 2006 and healthcare facility exposure information were collected. CDI cases were classified as hospital-onset (HO) if they were diagnosed > 48 hours after admission or community-onset/healthcare facility-associated if they were diagnosed ≤ 48 hours from admission and had recently been discharged from the healthcare facility. Four surveillance definitions were compared: HO cases only and HO plus community-onset/healthcare facility-associated cases diagnosed within 30 (HCFA-30), 60 (HCFA-60) and 90 (HCFA-90) days after discharge from the study hospital. Monthly CDI rates were compared. Control charts were used to identify potential CDI outbreaks. RESULTS: The HCFA-30 rate was significantly higher than the HO rate at two healthcare facilities (p<0.01). The HCFA-30 rate was not significantly different from the HCFA-60 or HCFA-90 rates at any healthcare facility. The correlations between each healthcare facility’s monthly rates of HO and HCFA-30 CDI were almost perfect (range, 0.94–0.99, p<0.001). Overall, 12 time points had a CDI rate >3 SD above the mean, including 11 by the HO definition and 9 by the HCFA-30 definition, with discordant results at 4 time points (κ = 0.794, p<0.001). CONCLUSIONS: Tracking community-onset/healthcare facility-associated cases in addition to HO cases captures significantly more CDI cases but surveillance of HO CDI alone is sufficient to detect an outbreak