Immunofluorescent Localization Of Basement Membrane In Lesions Of Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is a blistering disease with a characteristic histology that includes papillary edema, neutrophilic papillary microabscesses, and development of subepidermal blisters. In spite of this pathologic sequence occurring entirely beneath the basement membrane zone, prior studies have indicated that the basement membrane, as defined by periodic acid-Schiff (PAS) or silver stains, lies at the floor of fully formed blisters or is destroyed by the disease process. To more accurately assess its location in primary lesions of DH, the basement membrane was stained using immunofluorescent techniques.Lesional skin from 5 patients with DH was used as substrate for indirect immunofluorescence with sera from patients with bullous pemphigoid (BP) and fluoresceinated antihuman IgG. The BP-stained basement membrane was attached to the roofs of early blisters, where it would be expected from the pathologic sequence of blister formation. PAS stains of the same or serial sections show the basement membrane to be in the roof or at the floor of the blisters. PAS stains of sections from formalin-fixed lesional skin, on the other hand, show the basement membrane to routinely lie at the blister floor, when not destroyed.The BP-stained epidermal basement membrane has greater anatomic and functional significance than either the PAS- or silver-stained basement membrane for two reasons: (1) it corresponds to a specific morphologic structure, the lamina lucida, a part of the epidermis, and remains attached to the rest of the epidermis unless destroyed; and (2) it is antigenic, capable of binding with BP antibodies

Identification of CD3+CD4−CD8− T Cells as Potential Regulatory Cells in an Experimental Murine Model of Graft-Versus-Host Skin Disease (GVHD)

We have developed K14-mOVA transgenic (Tg) mice that express membrane-associated ovalbumin (mOVA) under the control of a K14 promoter, as well as double Tg mice, by crossing them with OT-I mice that have a TCR recognizing the OVA peptide. When injected with CD8+ OT-I cells, K14-mOVA Tg mice develop graft-versus-host disease (GVHD), whereas double Tg mice are protected. This suggests that, in double Tg mice, regulatory mechanisms may prevent infused OT-I cells from inducing GVHD. We demonstrated that, after adoptive transfer, TCRαβ+CD3+CD4−CD8−NK1.1− double-negative (DN) T cells are increased in the peripheral lymphoid organs and skin of double Tg mice and exhibit a Vα2+Vβ5+TCR that has the same TCR specificity as OT-I cells. These DN T cells isolated from tolerant double Tg mice proliferated in response to OVA peptide and produced IFN-γ in the presence of IL-2. These cells could also suppress the proliferation of OT-I cells and were able to specifically kill activated OT-I cells through Fas/Fas ligand interaction. These findings suggest that DN T cells that accumulate in double Tg mice have regulatory functions and may have a role in the maintenance of peripheral tolerance in vivo

Antigen Presentation and Allogeneic Stimulation by Langerhans Cells

Isolated Langerhans cells were studied for 2 immunologic functions, the ability to present antigen to sensitized T lymphocytes and the ability to act as stimulator cells for mixed lymphocyte reactions. Langerhans cells can perform both of these functions. This fact, with the previous finding that Langerhans cells possess surface la antigens and Fe and C3 receptors, strongly suggests that Langerhans cells act as epidermal macrophages

The Appearance of Four Basement Membrane Zone Antigens in Developing Human Fetal Skin

In order to study the ontogeny of various structural and antigenic components of the basement membrane zone of human skin, we have examined skin specimens from 20 aborted fetuses ranging in gestational ages from 6 to 25 weeks, utilizing light microscopy, transmission electron microscopy, and indirect immunofluorescence with antibodies to bullous pemphigoid antigen, laminin, type IV collagen, and to the antigen defined by KF-1 monoclonal antibody. Both laminin and type IV collagen were detectable as early as 6 weeks of gestational age. In contrast, bullous pemphigoid antigen and the antigen defined by KF- 1 antibody were not detectable before 10 weeks and 16 weeks, respectively. The appearance of bullous pemphigoid antigen correlated with stratification of the epidermis and the formation of hemidesmosomes and anchoring fibrils at the basement membrane zone. KF- 1 antigen is first expressed when the epidermis is further stratified, hemidesmosomes and anchoring fibrils are present in greater numbers and with increased frequency at the dermal-epidermal junction, and hair follicles have begun to bud downward from the basal layer of the epidermis. Our findings suggest an orderly sequence to the appearance of these basement membrane zone components within human skin

Viral Studies In Pemphigus

Sera from patients with pemphigus. other bullous dermatoses, and various control groups were examined to determine whether paramyxoviruses, particularly SVS and DU, could be isolated. Indirect immunofluorescent tests and virus neutralization tests were employed to determine the incidence of SV5 virus antibody in sera from patients with various dermatoses, and to determine whether antibody to SV5 was related to the antiepithelial antibody associated with pemphigus. The frequency of antibody to SV5 (9%) and DU (11%) virus in sera from patients with pemphigus was not higher than the frequency ot antibodies to SV5 (14%) and DU (17%) in sera of various control groups. The absence of antibodies to 8V5 and DU virus in sera from most patients with pemphigus, the absence of intercellular antiepithelial antibody in sets from dogs and most humans with antibody to SV5 and DU virus, and the absence of correlation of titers in a patient with both types of antibody indicate that SV5 antibody is not functionally related to “pemphigus antibody.” In addition, no SV5, DU, or other hemadsorbing paramyxovirus was isolated from sera of patients with pemphigus. Isolation from blister fluid was not attempted. Infection with SV5, DU, or similar paramyxovirus is probably not usually, if at all, related to the etiology of non-Brazilian pemphigus

Ice-stream stability on a reverse bed slope

Marine-based ice streams whose beds deepen inland are thought to be inherently unstable. This instability is of particular concern because significant portions of the marine-based West Antarctic and Greenland ice sheets are losing mass and their retreat could contribute significantly to future sea-level rise. However, the present understanding of ice-stream stability is limited by observational records that are too short to resolve multi-decadal to millennial-scale behaviour or to validate numerical models8. Here we present a dynamic numerical simulation of Antarctic ice-stream retreat since the Last Glacial Maximum (LGM), constrained by geophysical data, whose behaviour is consistent with the geomorphological record. We find that retreat of Marguerite Bay Ice Stream following the LGM was highly nonlinear and was interrupted by stabilizations on a reverse-sloping bed, where theory predicts rapid unstable retreat. We demonstrate that these transient stabilizations were caused by enhanced lateral drag as the ice stream narrowed. We conclude that, as well as bed topography, ice-stream width and long-term retreat history are crucial for understanding decadal- to centennial-scale ice-stream behaviour and marine ice-sheet vulnerability

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

The Problem of Experience in the Study of Organizations

This paper deals with the fact that we cannot experience large organizations directly, in the same way as we can experience individuals or small groups, and that this non-experientiability has certain implications for our scientific theories of organizations. Whereas a science is animated by a constructive interplay of theory concepts and experience concepts, the study of organizations has been confined to theory concepts alone. Implications of this analysis for developing a science of organizations are considered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68303/2/10.1177_017084069301400102.pd