No abstract

The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling and induction of T cell–specific interferon (IFN)-γ expression in the development of T helper cell (Th)1–type pathology were examined in two different models of experimental colitis. In each model, abnormal reconstitution of the T cell compartment in immunodeficient mice by adoptive cell transfer leads to a wasting syndrome and inflammation of the colon, induced by IFN-γ and tumor necrosis factor (TNF)-α–producing T cells. We show here that treatment with anti–IL-12 antibodies in one of the models, or reconstitution with T cells from Stat-4–deficient (Stat-4null) mice in both models resulted in a milder disease in the majority of recipient animals, compared with those that were left untreated or that had been reconstituted with wt cells. Protected mice in each group also harbored lower frequencies of IFN-γ–producing T cells than did diseased mice, suggesting that effects on wasting and colitis resulted from the attenuation of IFN-γ expression by T cells. To test whether the development of pathogenic T cells in the two colitis models was directly dependent on T cell–specific IFN-γ expression, IFN-γnull donors were used for T cell reconstitution in each system. Surprisingly, large numbers of IFN-γnull–reconstituted mice developed wasting and colitis, which in many cases was of comparable severity to that seen in animals reconstituted with wt cells. Furthermore, T cells from these animals expressed TNF-α, demonstrating that they had retained the ability to produce another proinflammatory cytokine. Taken together, these results demonstrate that in some forms of chronic experimental colitis the development of pathogenic T cells is influenced predominantly, though not exclusively, by IL-12 via the actions of Stat-4 proteins. Furthermore, our data suggest that in the models of colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways are not limited to the induction of IFN-γ gene expression in T lymphocytes.

No abstract

The susceptibilities to arsenic and cadmium together with the detection of plasmid DNA were evaluated for use as epidemiological markers for the subtyping of Listeria monocytogenes. Plasmid DNA was detected in 34% of 322 apparently unrelated isolates of L. monocytogenes. The resistance to cadmium and arsenic differentiated 565 apparently unrelated cultures into four groups, the smallest being 5% of cultures resistant to both agents, and the largest (53%) being sensitive to cadmium and resistant to arsenic. The resistance patterns to these agents and the presence of plasmid DNA varied markedly between the serotypes of the cultures. The detection of plasmid DNA was strongly associated with cadmium resistance in serogroup 1/2 cultures, but not within those of serogroup 4. Arsenic resistance was not associated with plasmid DNA. All methods were sufficiently stable to be useful for epidemiological investigations. The techniques described here offer simple methods which can be easily utilized in laboratories without a specialized expertise for this bacterium.

We have previously reported that oral biofilms in clinically healthy smokers are pathogen-rich, and that this enrichment occurs within 24 h of biofilm formation. The present investigation aimed to identify a mechanism by which smoking creates this altered community structure. By combining in vitro microbial-mucosal interface models of commensal (consisting of Streptococcus oralis, Streptococcus sanguis, Streptococcus mitis, Actinomyces naeslundii, Neisseria mucosa and Veillonella parvula) and pathogen-rich (comprising S.oralis, S.sanguis, S.mitis, A.naeslundii, N.mucosa and V.parvula, Fusobacterium nucleatum, Porphyromonas gingivalis, Filifactor alocis, Dialister pneumosintes, Selenonomas sputigena, Selenominas noxia, Catonella morbi, Parvimonas micra and Tannerella forsythia) communities with metatranscriptomics, targeted proteomics and fluorescent microscopy, we demonstrate that smoke exposure significantly downregulates essential metabolic functions within commensal biofilms, while significantly increasing expression of virulence genes, notably lipopolysaccharide (LPS), flagella and capsule synthesis. By contrast, in pathogen-rich biofilms several metabolic pathways were over-expressed in response to smoke exposure. Under smoke-rich conditions, epithelial cells mounted an early and amplified pro-inflammatory and oxidative stress response to these virulence-enhanced commensal biofilms, and a muted early response to pathogen-rich biofilms. Commensal biofilms also demonstrated early and widespread cell death. Similar results were observed when smoke-free epithelial cells were challenged with smoke-conditioned biofilms, but not vice versa. In conclusion, our data suggest that smoke-induced transcriptional shifts in commensal biofilms triggers a florid proinflammatory response, leading to early commensal death, which may preclude niche saturation by these beneficial organisms. The cytokine-rich, pro-oxidant, anaerobic environment sustains inflammophilic bacteria, and, in the absence of commensal antagonism, may promote the creation of pathogen-rich biofilms in smokers.

Background Despite the fact that the inflammatory bowel diseases (IBD) and their treatments may affect physical appearance, the effect of IBD on body image is poorly understood. The aims of this study were to determine whether body image dissatisfaction (BID) changes over time in patients with IBD and to examine the demographic and disease-related variables associated with decreased body image. Methods Adults aged 18 and above in the Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. BID was assessed using a modified version of the Adapted Satisfaction With Appearance (ASWAP) questionnaire. Total ASWAP scores and 2 sub-scores were calculated. To assess for changes over time, general linear models for correlated data were used for continuous outcomes and generalized estimating equations were used for discrete outcomes. Results Two hundred seventy-four patients were studied. BID was found to be stable over time among men and women with IBD despite overall improvements in disease activity. No differences were found in BID according to IBD subtype. Female gender, greater disease activity, higher symptom burden, longer duration of steroid use, dermatologic and musculoskeletal manifestations of IBD, and ileocolonic disease location among patients with Crohn's disease were associated with greater BID. Greater BID was associated with lower health-related quality of life (HRQOL). Conclusions BID remains stable in an incident cohort of IBD despite improved disease activity and is associated with lower HRQOL

No abstract

No abstract