Human T cells that have been conditioned by the proteolytic activity of the major dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B cells

BACKGROUND: We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa alpha subunit of the IL-2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN-gamma and more IL-4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis. OBJECTIVE: To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells. METHODS: We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored. RESULTS: Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses. CONCLUSIONS: The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells.     

Potentiation of in vitro synthesis of human IgE by cyclosporin A (CsA).

In this study, we investigated the modulatory effects of CsA on in vitro synthesis of IgE, IgG1 and IgG4 by human peripheral blood mononuclear cells (PBMC). In contrast to its known immunosuppressive effect, we have demonstrated that a low dose of CsA (10(-7) M, 120 ng/ml) potentiated IgE production by up to 40-fold (i.e. from 33 +/- 4.5 to 1346 +/- 290 ng/ml). This potentiation was specific for IgE since no such effect was demonstrable with IgG1 and IgG4. Potentiation of IgE synthesis by CsA in the PBMC cultures was partly due to CsA acting on T cells, as demonstrated by the addition of CsA-treated T cells to T cell-depleted cultures. However, potentiation was also demonstrable in a T cell-depleted, anti-CD40-stimulated culture (four-fold increase from 400 +/- 48 to 1606 +/- 127 ng/ml). Our data therefore suggest that there are at least two mechanisms for CsA-induced potentiation of IgE synthesis, one T cell-dependent and the other T cell-independent. The clinical implications of these findings are discussed with regard to the use of CsA in the treatment of Th2-mediated diseases.     

Development of a novel explant culture method for the isolation of mesenchymal stem cells from human breast tumor

Background: Mesenchymal stem cells (MSCs) were isolated from various sources, including various types of tumors. However choosing an appropriate isolation method is an important step in obtaining cells with optimal quality and yield in companion with economical considerations. The purpose of this study was to isolate more pure MSCs from human breast tumor tissue by a modified explant culture method.

Methods and Materials: The tumor tissues (n = 8) were cut into 1 to 3-mm cube-like pieces (explant). Each explant was placed in a well of 24-well format plates, cultured in Dulbecco’s Modified Eagle’s medium (DMEM), and maintained at 37°C with 5% humidified incubator. Morphological phenotypes of the cells were surveyed by an inverted microscope and wells with rather homogenous fibroblast-like morphology cell were considered as positive and selected for more expansion and characterization.

Results: A total of 185 wells, 63.7% of wells were positive that were chosen for expansion. Flowcytometry analysis demonstrated that isolated cells were positive for CD73, CD44, CD29, CD105, and CD90 but negative for CD11b, CD45, CD34, and HLA?DR. In addition, cells possessed the capability of multipotential differentiation into osteoblasts and adipocytes.     

Heart failure after conventional metal-on-metal hip replacements

Background and purpose — It is unclear whether metal particles and ions produced by mechanical wear and corrosion of hip prostheses with metal-on-metal (MoM) bearings have systemic adverse effects on health. We compared the risk of heart failure in patients with conventional MoM total hip arthroplasty (THA) and in those with metal-on-polyethylene (MoP) THA.

Patients and methods — We conducted a retrospective cohort study using data from the Australian Government Department of Veterans’ Affairs health claims database on patients who received conventional THA for osteoarthritis between 2004 and 2012. The MoM THAs were classified into groups: Articular Surface Replacement (ASR) XL Acetabular System, other large-head (LH) (> 32?mm) MoM, and small-head (SH) (≤ 32?mm) MoM. The primary outcome was hospitalization for heart failure after THA.

Results — 4,019 patients with no history of heart failure were included (56% women). Men with an ASR XL THA had a higher rate of hospitalization for heart failure than men with MoP THA (hazard ratio (HR)?=?3.2, 95% CI: 1.6–6.5). No statistically significant difference in the rate of heart failure was found with the other LH MoM or SH MoM compared to MoP in men. There was no statistically significant difference in heart failure rate between exposure groups in women.

Interpretation — An association between ASR XL and hospitalization for heart failure was found in men. While causality between ASR XL and heart failure could not be established in this study, it highlights an urgent need for further studies to investigate the possibility of systemic effects associated with MoM THA.     

Hydrophilic polymer microemboli in a patient with a chronic cutaneous ulcer: a case report

Hydrophilic polymer coatings were designed to reduce friction between the catheter and vessel wall and facilitate intravascular manipulations during catheterization and placement of drug‐eluting stents. One newly reported complication of such hydrophilic coatings is the fragmentation and embolization of the polymer, which can lead to ischemia and infarct by blocking the small vasculature. In this report, we present a patient with a non‐healing ulcer on the leg. Biopsy from the ulcer revealed the presence of hydrophilic polymer emboli within the dermal vessels. This is one of the few reports of such a complication involving the skin. Our objective is to emphasize the histopathologic features of this uncommon iatrogenic phenomenon.