HLA homology within the C5 domain promotes peptide binding by HIV type 1 gp120

The mechanisms by which HIV-1 induces chronic pathogenic immune activation associated with disease progression remain unclear despite many years of AIDS research. One proposal suggests that sequence and structural mimicry between gp120 and HLA may endow HIV with the capacity to arouse alloreactive and autoimmune responses within the susceptible host, fueling disease progression in a manner similar to graft-versus-host disease (GVHD). Both gp120 and HLA share a common functional interaction with CD4 but also demonstrate peptide binding properties. Here we report the conserved nature of this feature across HIV-1 envelopes, the crucial role of the HLA homologous C5 region for peptide interactions, and the elimination of this property through specific antibody targeting. Given that the C5 domain mimics a HLA activation domain and the reported clinical benefits associated with nonneutralizing antibodies against this region, targeting the C5 domain may have use as a therapeutic vaccine to protect against disease progression.     

The epidemiology of Helicobacter pylori infection in African refugee children resettled in Australia

OBJECTIVE: To determine the prevalence and associated epidemiological features of Helicobacter pylori infection in child refugees in Western Australia. DESIGN AND PARTICIPANTS: Cross-sectional study of 193 eligible African refugee children (aged < 16 years) at their initial health assessment after resettlement in Australia between 1 February and 30 November 2006. MAIN OUTCOME MEASURES: (i) Prevalence of H. pylori infection determined by monoclonal faecal antigen enzyme immunoassay testing (MFAT); (ii) associations of H. pylori infection with epidemiological factors (age, sex, transit through refugee camps, comorbidities and treatment interventions). RESULTS: MFAT was performed in 182 of the 193 children; 149 of these 182 (82%) had H. pylori infection. Age was an independent predictor of H. pylori infection (odds ratio [OR], 1.18; 95% CI, 1.07-1.31). No sex differences were observed. Premigration antimalarial therapy (with sulfadoxine-pyrimethamine and artesunate) significantly reduced the prevalence of H. pylori infection (age-adjusted OR, 0.33; 95% CI, 0.15-0.75). CONCLUSION: African refugee children have a high prevalence of H. pylori infection. Increasing age is a strong predictor of infection and antimalarial treatment may have a protective effect.     

Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein

Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, P<0.0001), increased transvalvular velocity and transvalvular pressure gradient (both P<0.01 via 2-way ANOVA) compared to the control group. There was associated valve calcification, lipid deposition and macrophage infiltration. Endothelial function was markedly impaired, and intravalvular TXNIP concentration increased. In this model, vitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.     

Quantitative CEST and MT at 1.5T for monitoring treatment response in glioblastoma: early and late tumor progression during chemoradiation

Journal of Neuro-Oncology - Quantitative MRI (qMRI) was performed using a 1.5T protocol that includes a novel chemical exchange saturation transfer/magnetization transfer (CEST/MT) approach. The...