Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo

The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of antitumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit antitumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were cocultured with bone marrow-derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs cocultured with mAb-coated tumor cells were protected from tumor challenge (60% long-term survival), whereas DCs loaded with tumor cells alone were much less effective. The opsonized whole tumor cell-DC vaccine elicited significantly better tumor protection than a traditional lymphoma idiotype (Id) protein vaccine, and in combination with chemotherapy could eradicate preexisting tumor. Moreover, the DC vaccine protected animals from both wild-type and Id-negative variant tumor cells, indicating that Id is not a major target of the induced tumor immunity. Protection was critically dependent upon CD8(+) T cells, with lesser contribution by CD4(+) T cells. Importantly, opsonized whole tumor cell-DC vaccination did not result in tissue-specific autoimmunity. Since opsonized whole tumor cell-DC and Id vaccines appear to target distinct tumor antigens, optimal antilymphoma immunity might be achieved by combining these approaches.     

Exercise, insulin resistance, and hypertension: a complex relationship

More than 300,000 deaths occur annually in the United States alone as a result of obesity, poor dietary habits, or physical inactivity. Obesity is now an increasingly recognized independent risk factor for cardiovascular disease and leads to numerous other comorbidities. The causal relationships between obesity and both insulin resistance and hypertension have been consistently demonstrated in numerous studies. The relationships consist of cascading events involving insulin, leptin, adiponectin, and other hormones that often precipitate the development of metabolic syndrome. As we learn more about the metabolic activity of the adipose tissue, we can better identify the mechanisms that associate weight reduction with a decrease in health risks. Evidence suggests that exercise produces a positive effect on weight reduction, insulin sensitivity, and blood pressure. Therefore, weight reduction and therapeutic changes in lifestyle should be encouraged in all overweight and obese patients. It is imperative to increase the awareness of the obesity epidemic and to emphasize the importance of exercise as both treatment and prevention of metabolic disease.     

Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling

OBJECTIVE: To determine whether hydralazine might decrease DNA methyltransferase (DNMT) expression and induce autoimmunity by inhibiting extracellular signal-regulated kinase (ERK) pathway signaling. METHODS: The effect of hydralazine on DNMT was tested in vitro using enzyme inhibition studies, and in vivo by measuring messenger RNA (mRNA) levels and enzyme activity. Effects on ERK, c-Jun N-terminal kinase, and p38 pathway signaling were tested using immunoblotting. Murine T cells treated with hydralazine or an ERK pathway inhibitor were injected into mice and anti-DNA antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: In vitro, hydralazine did not inhibit DNMT activity. Instead, hydralazine inhibited ERK pathway signaling, thereby decreasing DNMT1 and DNMT3a mRNA expression and DNMT enzyme activity similar to mitogen-activated protein kinase kinase (MEK) inhibitors. Inhibiting T cell ERK pathway signaling with an MEK inhibitor was sufficient to induce anti-double-stranded DNA antibodies in a murine model of drug-induced lupus, similar to the effect of hydralazine. CONCLUSION: Hydralazine reproduces the lupus ERK pathway signaling abnormality and its effects on DNMT expression, and inhibiting this pathway induces autoimmunity. Hydralazine-induced lupus could be caused in part by inducing the same ERK pathway signaling defect that occurs in idiopathic lupus.     

Dual-scale TiO2 and SiO2 particles in combination with a fluoroalkylsilane and polydimethylsiloxane superhydrophobic/superoleophilic coating for efficient solvent–water separation

Surfaces that have unique wettabilities and are simultaneously superhydrophobic with water contact angles > 150°, and superoleophilic with oil contact angles < 5°, are of critical importance in the oil/solvent–water separation field. This work details the facile preparation of highly efficient oil–water separation devices that successfully combine hierarchical surface roughening particles and low surface energy components with porous substrates. Coatings were generated using TiO₂ and hydrophobic-SiO₂ micro/nanoparticle loadings which were then embedded within polydimethylsiloxane, commercially known as Sylgard® 184, and 1H,1H,2H,2H-perfluorooctyltriethoxysilane (FAS) polymer mixtures. The resulting slurries were dip coated onto copper meshes with varying pore diameters (30, 60 and 100 meshes had 595, 250 and 149 μm pore dimensions respectively). Functional testing proved that mesh substrates coated in the lowest Sylgard® 184 : FAS polymer ratio formulations displayed heightened water repellency and retained their superoleophilic properties upon repeat testing. The largest average water contact angle of 145 ± 1°, was recorded on a copper 30 mesh substrate with a coating comprising H-SiO₂ microparticles and TiO₂ nanoparticles in a 1 : 9 polymer mixture of Sylgard® and FAS. The coating''s extreme oil affinity was supported by high solvent–water separation efficiencies (≥99%) which withstood numerous testing/washing cycles.

Surfaces that have unique wettabilities and are simultaneously superhydrophobic with water contact angles > 150°, and superoleophilic with oil contact angles < 5°, are of critical importance in the oil/solvent–water separation field.     

Observations on the ligand selectivity of the melanocortin 2 receptor

The melanocortin 2 receptor (MC2R) is unique in terms of ligand selectivity and in vitro expression in mammalian cell lines as compared to the other four mammalian MCRs. It is well established that ACTH is the only melanocortin ligand that can activate the ACTH receptor (i.e., melanocortin 2 receptor). Recent studies have provided new insights into the presence of a common binding site for the HFRW motif common to all melanocortin ligands. However, the activation of the melanocortin 2 receptor requires an additional amino acid motif that is only found in the sequence of ACTH. This mini-review will focus on these two topics and provide a phylogenetic perspective on the evolution of MC2R ligand selectivity.     

Effectiveness of a school-based intervention to increase health knowledge of cardiovascular disease risk factors among rural Mississippi middle school children

BACKGROUND: Few school-based interventions have been evaluated to assess health awareness among children in rural southern areas. The purpose of this controlled investigation was to increase health awareness among middle school-aged children residing in a racially diverse rural community in Mississippi. METHODS: This investigation assessed health knowledge before and after a 16-week school-based intervention in 205 fifth-grade students. Height, weight, BMI, body composition, waist circumference, dietary intake, blood lipids and lipoprotein concentrations, blood glucose concentrations, and resting blood pressure were measured to enhance student awareness of cardiovascular disease risk factors. Values in the intervention school were compared with those obtained simultaneously in a control school within the same community. RESULTS: The school-based intervention was effective in increasing health knowledge in the intervention as compared with the control school. Secondarily, it was effective in improving certain dietary behaviors. Utilizing health care professionals in the classroom to teach students appropriate lifestyles and actually measuring cardiovascular risk factors to increase awareness among students was effective in increasing overall health knowledge. CONCLUSIONS: Health knowledge of rural adolescents can be increased through partnerships with schools and multidisciplinary teams of health care professionals. Ongoing efforts to reduce childhood obesity and cardiovascular disease risk factors are urgently needed, and information obtained during this investigation may be used in planning school-based interventions in other diverse, rural communities.     

Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? Study of cellular proliferation markers

Recent research suggests that allergy may be the key factor in the etiology of eosinophilic esophagitis (EE); however, historically, the condition was hypothesized as related to reflux injury to the esophageal mucosa. We studied this hypothesis by comparing markers of inflammation and cellular proliferation in EE and reflux esophagitis. Lower esophageal biopsies of adult patients with EE ( n  = 10), reflux esophagitis ( n  = 8), and normal controls ( n  = 13) were assessed quantitatively for the expression of the cyclooxygenase-2 (COX-2) enzyme, cellular proliferation, and oncogenic resistance to apoptosis using monoclonal antibodies for COX-2, Ki-67, and Bcl-2, respectively. Normal esophageal epithelium demonstrated weak diffuse uptake of COX-2 stain in the basal layer. No COX-2 expression was demonstrated in the EE group, significantly less than the control and reflux groups ( P  < 0.01 and P  < 0.001, respectively). Cellular proliferation measured by Ki-67 expression was higher in EE and reflux compared with control ( P  < 0.001 and P  < 0.01). Ki-67 expression, and thus degree of hyperplasia, appeared greater in EE than reflux, but was not statistically significant ( P  = 0.228). The degree of apoptosis was similar in all study groups. EE and reflux esophagitis are proliferative conditions expressing Ki-67 in higher concentrations than control. Mucosal proliferation in reflux esophagitis is COX-2 dependent. This novel research in EE has demonstrated downregulation of COX-2 expression compared with reflux esophagitis and control. We hypothesize that the allergy-related cytokine IL-13 known to inhibit COX-2 expression and found in high concentrations in EE as responsible for this. The pathogenesis of EE is likely dependent on allergy rather than reflux injury to the esophagus.