Early gene expression changes with rush immunotherapy

<p>Abstract</p> <p>Background</p> <p>To examine whether whole genome expression profiling could reveal changes in mRNA expression of peripheral blood mononuclear cells (PBMC) from allergic patients undergoing rush immunotherapy (RIT) that might be manifest within the first few months of treatment.</p> <p>Methods</p> <p>For this study, PBMC from three allergic patients undergoing RIT were assessed at four timepoints: prior to RIT, at 1 week and 7 week post-RIT, during build-up and at 4 months, after establishment of a maintenance dose. PBMC mRNA gene expression changes over time were determined by oligonucleotide microarrays using the Illumina Human-6 BeadChip Platform, which simultaneously interrogates expression profiles of > 47,000 transcripts. Differentially expressed genes were identified using well-established statistical analysis for microarrays. In addition, we analyzed peripheral blood basophil high-affinity IgE receptor (Fc epsilon RI) expression and T-regulatory cell frequency as detected by expression of CD3⁺CD4⁺CD25bright cells at each timepoint using flow cytometry.</p> <p>Results</p> <p>In comparing the initial 2 timepoints with the final 2 timepoints and analyzing for genes with ≥1.5-fold expression change (p less than or equal to 0.05, BH-FDR), we identified 507 transcripts. At a 2-fold change (p less than or equal to 0.05, BH-FDR), we found 44 transcripts. Of these, 28 were up-regulated and 16 were down-regulated genes. From these datasets, we have identified changes in immunologically relevant genes from both the innate and adaptive response with upregulation of expressed genes for molecules including IL-1β, IL-8, CD40L, BTK and BCL6. At the 4 month timepoint, we noted a downward trend in Fc epsilon RI expression in each of the three patients and increased allergen-specific IgG4 levels. No change was seen in the frequency of peripheral T-regulatory cells expressed over the four timepoints.</p> <p>Conclusions</p> <p>We observed significant changes in gene expression early in peripheral blood samples from allergic patients undergoing RIT. Moreover, serum levels for allergen specific IgG4 also increased over the course of treatment. These studies suggest that RIT induces rapid and dynamic alterations in both innate and adaptive immunity which can be observed in the periphery of allergic patients. These alterations could be directly related to the therapeutic shift in the allergen-specific class of immunoglobulin.</p

Transcriptome Alteration in the Diabetic Heart by Rosiglitazone: Implications for Cardiovascular Mortality

BACKGROUND: Recently, the type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling and imaging studies of a murine model of type 2 diabetes, the C57BL/KLS-lepr(db)/lepr(db) (db/db) mouse. METHODS AND FINDINGS: We compared cardiac gene expression profiles from three groups: untreated db/db mice, db/db mice after rosiglitazone treatment, and non-diabetic db/+ mice. Prior to sacrifice, we also performed cardiac magnetic resonance (CMR) and echocardiography. As expected, overall the db/db gene expression signature was markedly different from control, but to our surprise was not significantly reversed with rosiglitazone. In particular, we have uncovered a number of rosiglitazone modulated genes and pathways that may play a role in the pathophysiology of the increase in cardiac mortality as seen in several recent meta-analyses. Specifically, the cumulative upregulation of (1) a matrix metalloproteinase gene that has previously been implicated in plaque rupture, (2) potassium channel genes involved in membrane potential maintenance and action potential generation, and (3) sphingolipid and ceramide metabolism-related genes, together give cause for concern over rosiglitazone's safety. Lastly, in vivo imaging studies revealed minimal differences between rosiglitazone-treated and untreated db/db mouse hearts, indicating that rosiglitazone's effects on gene expression in the heart do not immediately turn into detectable gross functional changes. CONCLUSIONS: This study maps the genomic expression patterns in the hearts of the db/db murine model of diabetes and illustrates the impact of rosiglitazone on these patterns. The db/db gene expression signature was markedly different from control, and was not reversed with rosiglitazone. A smaller number of unique and interesting changes in gene expression were noted with rosiglitazone treatment. Further study of these genes and molecular pathways will provide important insights into the cardiac decompensation associated with both diabetes and rosiglitazone treatment

Cobalt-substituted iron-based wolframite synthesized via polyol route for efficient oxygen evolution reaction

International audienc

Hiatal hernia involving prolapse of the entire stomach into the mediastinum after distal gastrectomy: a case report

Abstract Background Prolapse of a small part of the proximal stomach through the hiatus into the mediastinum is relatively common. Hiatal hernia involving the postoperative stomach has been reported previously, but the degree of hernia was not so severe, and hiatal hernia involving the prolapse of the entire stomach following gastrectomy into the mediastinum has never been reported. We describe a very rare case of large hiatal hernia involving the entire postoperative stomach. Case presentation A 79-year-old man with a history of distal gastrectomy for submucosal benign tumor 40 years ago was referred to our hospital because of dysphagia and weight loss. Computed tomography revealed prolapse of the entire postoperative stomach into the mediastinum, and a radical operation was performed. There was a strong adhesion in the hernial sac of the mediastinum, but only little adhesion due to a previous open surgery in the abdominal cavity was present. After the stomach was pulled into the abdominal cavity, suture cruroplasty and Toupet fundoplication without dissection of the short gastric artery were performed. The patient experienced postoperative paralytic ileus, but the rest of the postoperative course was uneventful and the symptom of dysphagia improved. Conclusions We presented a very rare large hiatal hernia involving the entire postoperative stomach. Toupet fundoplication preserving the short gastric artery could be one of the optimal surgeries to prevent postoperative regurgitation of the remnant stomach

Cobalt-Doped Goethite-Type Iron Oxyhydroxide (α-FeOOH) for Highly Efficient Oxygen Evolution Catalysis

It is an urgent challenge to develop low-cost and high-performance catalysts for the oxygen evolution reaction (OER). We synthesized nanoparticulate electrocatalysts consisting of cobalt-doped goethite-type iron oxyhydroxide (α-FeOOH) with controlled Co/Fe ratios [Co_<i>x</i>Fe_1–<i>x</i>OOH (<i>x</i> ≤ 0.20)] based on our own wet process. A Co_0.20Fe_0.80OOH-coated glassy carbon electrode generated a current density (<i>j</i>) of 10 mA cm^–2 at an overpotential (η) as small as 383 mV (1.61 V vs the reversible hydrogen electrode) in an alkaline electrolyte, with a small Tafel slope of 40 mV dec^–1 and excellent durability, whereas pure α-FeOOH required η = 580 mV to reach the same current density. This can be ascribed to the effect of Co doping, which resulted in an increase in electrochemically active surface area and a decrease in charge-transfer resistance. The content of cobalt, a scarce resource, in the catalyst is much smaller than those in most of the other Fe-based catalysts reported so far. Thus, this study will provide a new strategy of designing cost-effective and high-performance catalysts for the OER in alkaline solution