Demonstration of Pemphigus Antibodies on the Cell Surface of Murine Epidermal Cell Monolayers and their Internalization

The pathogenic effects of pemphigus vulgaris (PV) antibodies on epidermal cells can be demonstrated both in vitro using skin organ culture or primary epidermal cell cultures (PECC) and in vivo by passive transfer of PV antibodies into neonatal BALB/c mice. Although PV antibodies have been localized on the epidermal cell surface by several techniques, little is known about the fate of these autoantibodies subsequent to their surface binding. We have examined this, using murine PECC which express pemphigus antigen on their surface, and followed the fate of the bound antibody molecules. Forty-eight-hour PECC were incubated at 37°C with PV antibodies for 20 min and then with horseradish peroxidase-labelled antihuman IgG. This was considered time 0. The monolayers were fixed with glutaraldehyde after 0, 0.5, 1, 3, 6, 18, and 24 h incubation at 37°C and then processed for electron microscopy. At time 0 hour, PV antibodies is detected bound evenly along the surface of keratinocytes. Within 30 min, the bound PV antibodies becomes clustered, internalized into submembranous vesicles via surface pits, and eventually fused with lysosomes. Widening of the intercellular spaces was also seen in PECC treated with PV antibodies within the first 24 h. PECC treated with normal human IgG in parallel cultures showed no such surface binding, internalization, or cell-cell detachment. Treatment with cytochalasin-D and/or colchicine did not affect the internalization of the PV antibodies, but fusion with lysosomes was not seen in treated cultures.These findings suggest that PV antibodies binds a surface antigen and the complex is internalized and fused with lysosomes in a process that may have pathophysiologic relevance

Elderly people and the boundary between health and social care 1946-91 Whose responsibility?

SIGLEAvailable from British Library Document Supply Centre-DSC:6184.41325(no 1) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Polybrominated diphenyl ethers and perfluorinated alkyl substances in blood serum of New Zealand adults, 2011-2013

A national survey was conducted in 2011-2013 to assess serum concentrations of brominated flame retardants (BFRs) and perfluorinated alkyl substances (PFASs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 geographic regions, 2 ethnic groups (Māori/non-Māori) and sex. Eligible participants (n = 734; response rate of contacted individuals = 37%) donated up to 30 mL of blood, after which serum was pooled (49 pools for BFRs, 63 pools for PFASs) according to demographic strata. BFRs were analysed by GC-HRMS and PFASs by LC-MS/MS. Associations between serum BFRs and PFASs and demographic variables (age, region, ethnicity, sex) were assessed using regression analysis. The weighted geometric mean (GM) serum concentrations of BDE47, BDE99, BDE100, and BDE153 were 2.0, 0.66, 0.43, and 1.2 ng/g lipid, respectively. The weighted geometric mean (GM) serum concentrations of PFOS, PFOA, PFHxS, and PFNA were 3.4, 2.4, 1.0, and 0.66 ng/mL, respectively. The majority of BFRs showed higher serum concentrations in younger age groups. Conversely, the four PFASs showed higher serum concentrations in older age groups. Concentrations of BFRs and PFASs were generally lower in females compared to males. In New Zealand, both age and sex are important determinants of BFR and PFAS serum concentrations