NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions

The spectrum of cutaneous adverse drug reactions (cADRs) ranges from benign presentations to severe life-threatening forms such as toxic epidermal necrolysis (TEN). In TEN, granulysin has been shown to be the key cytotoxic molecule. Still, little is known about the expression of granulysin in other cADRs. As an important source of granulysin, natural killer (NK) cells are of major interest in cADRs. Recently, NKp46 has been identified as the most selective NK-cell marker. However, the role of NKp46(+) cells in cADRs and their contribution to granulysin expression remain to be elucidated.

Contemporary Hollywood And The Attention Economy

This thesis had two goals: to explore the transformation of Hollywood from the 1930s to present, and to investigate how Contemporary Hollywood functions in a growing attention economy. Evident in the types of films that it produces as well as its evolving industrial structure, Contemporary Hollywood significantly differs from the Classical Hollywood of the 1930s. New digital technologies like surround sound and computer-generated imagery (CGI) have allowed studios to create a different type of film like the blockbuster and to have more extensive control over their films. Additionally, growing exhibition and distribution platforms have also fundamentally altered the industrial landscape of Hollywood. In order to combat this more egalitarian distribution system, Contemporary Hollywood has turned to conglomeratization. But, what has caused such a radical shift in the form and function of Contemporary Hollywood and its films? This thesis argues that Hollywood is failing to thrive in this new media landscape¿not because of changing technologies¿but because of a changing consumer. Richard Lanham theorizes that we are living in a growing attention economy, where human attention is the most valuable commodity in such an information-saturated society. For the current consumer, there is near-constant media over-stimulation: he or she is exposed to any number of screens (mobile phones, laptops, tablets, televisions, etc.) at any given time. Because we can access anything from anywhere at anytime, we¿ve become somewhat schizophrenic and impatient in terms of the media that we consume in our lives.

Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage

Stem cell regeneration of damaged tissue has recently been reported in many different organs. Since the loss of retinal pigment epithelium (RPE) in the eye is associated with a major cause of visual loss - specifically, age-related macular degeneration - we investigated whether hematopoietic stem cells (HSC) given systemically can home to the damaged subretinal space and express markers of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were used in a sodium iodate (NaIO(3)) model of RPE damage in the mouse. The optimal time for adoptive transfer of bone marrow-derived stem cells relative to the time of injury and the optimal cell type [whole bone marrow, mobilized peripheral blood, HSC, facilitating cells (FC)] were determined by counting the number of GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65. The time at which bone marrow-derived cells were adoptively transferred relative to the time of NaIO(3) injection did not significantly influence the number of cells that homed to the subretinal space. At both one and two weeks after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were observed in the damaged subretinal space, at sites of RPE loss, but not in the normal subretinal space. The combined transplantation of HSC+FC cells appeared to favor the survival of the homed stem cells at two weeks, and RPE-65 was expressed by adoptively transferred HSC by four weeks. We have shown that systemically injected HSC homed to the subretinal space in the presence of RPE damage and that FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65 was expressed on adoptively transferred HSC in the denuded areas.

Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage

PURPOSE: The aim of the present study was to investigate whether bone marrow-derived cells (BMCs) can be induced to express retinal pigment epithelial (RPE) cell markers in vitro and can home to the site of RPE damage after mobilization and express markers of RPE lineage in vivo. METHODS: Adult RPE cells were cocultured with green fluorescence protein (GFP)-labeled stem cell antigen-1 positive (Sca-1(+)) BMCs for 1, 2, and 3 weeks. Cell morphology and expression of RPE-specific markers and markers for other retinal cell types were studied. Using an animal model of sodium iodate (NaIO(3))-induced RPE degeneration, BMCs were mobilized into the peripheral circulation by granulocyte-colony stimulating factor, flt3 ligand, or both. Immunocytochemistry was used to identify and characterize BMCs in the subretinal space in C57BL/6 wild-type (wt) mice and GFP chimeric mice. RESULTS: In vitro, BMCs changed from round to flattened, polygonal cells and expressed cytokeratin, RPE65, and microphthalmia transcription factor (MITF) when cocultured in direct cell-cell contact with RPE. In vivo, BMCs were identified in the subretinal space as Sca-1(+) or c-kit(+) cells. They were also double labeled for GFP and RPE65 or MITF. These cells formed a monolayer on the Bruch membrane in focal areas of RPE damage. CONCLUSIONS: Thus, it appears that BMCs, when mobilized into the peripheral circulation, can home to focal areas of RPE damage and express cell markers of RPE lineage. The use of endogenous BMCs to replace damaged retinal tissue opens new possibilities for cell replacement therapy in ophthalmology.