Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.
La pandemia mundial de la COVID-19 ha llevado a la suspensión de la actividad docente en muchos países. En el ámbito universitario la transformación urgente de las clases presenciales a un formato online se ha llevado a cabo de una forma que se puede calificar como aceptable en términos generales, si bien las medidas tomadas se han ajustado a la urgencia y no a una planificación pensada a priori para impartir una asignatura con una metodología completamente online. Afrontar una evaluación online masiva es algo a lo que las universidades de corte presencial no se habían enfrentado nunca desde una perspectiva institucional. El profesorado y el estudiantado, por tanto, tienen que colaborar para dar una respuesta que integre decisiones metodológicas y tecnológicas, a la vez que garantice la equidad, la seguridad jurídica y la transparencia para todos los actores, internos y externos. El Grupo de Responsables de Docencia Online de las Universidades Públicas de Castilla y León ha elaborado una guía de recomendaciones para ayudar al profesorado y a las universidades en este proceso. La esencia de esta guía se presenta en este artículo para hacer llegar estas recomendaciones al gran número de docentes que comparten este problema en este momento excepcional en todo el planeta.
Corneal epithelial-like cells can be induced from extraocular hAT-MSCs by subjecting them to an in vitro microenvironment containing conditioning signals derived from differentiated human corneal epithelial cells. Our results suggest that hAT-MSCs could provide a novel source of stem cells that hold the potential to restore sight lost in patients suffering from bilateral ocular surface failure due to LSCD.
SUMMARYImmunomodulatory effects of different retinoids have been demonstrated, both in vivo and in vitro, in different cellular lineages including human and murine thymocytes, human lung fibroblasts, Langerhans' cells, tumoral cells and natural killer (NK ) cells; however, any attempt to demonstrate the effect of retinoids on human peripheral blood mononuclear cells (PBMC ) resulted in negative results. In the present work, it is shown that retinol and retinoic acid induce a marked increase of proliferation on human PBMC from 32 unrelated healthy individuals, which had previously been stimulated with anti-CD3 antibodies 48 hr before. Serum-free medium, specific retinoid concentration (10−7 ) and a particular timing of retinol addition to the cultures (48 hr after CD3 stimulation) was necessary clearly to detect this retinol-enhancing effect. The increased proliferative response is specifically mediated via the clonotipic T-cell receptor-CD3 complex and correlates with the up-regulation of certain adhesion/activation markers on the T-lymphocyte surface: CD18, CD45RO and CD25; also Th1-type of cytokines (interleukin-2 and interferon-c) are found concordantly increased after retinoid costimulation, both measured by a direct protein measurement and by a specific mRNA increase. In addition, it is shown that the in vitro retinol costimulation is only present in immunodeficient patients who have no defect on CD3 molecules and activation pathway. The fact that retinol costimulate lymphocytes only via CD3 (and not via CD2 or CD28) and the lack of response enhancement in immunodeficients with impaired CD3 activation pathway indicates that retinoids may be used as therapeutic agents in immune system deficiencies that do not affect the clonotypic T-cell receptor.
Gamma interferon (IFN-␥) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-␥ receptor ligand-binding chain (IFN-␥R1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-␥R1 ligandbinding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN-␥ (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN-␥ receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.Gamma interferon (IFN-␥) is a widely studied cytokine and one of the most promising biological agents, with great therapeutic potential for several pathologies. This is mainly due to its immunomodulatory and antiproliferative effects and, probably, to its antiviral capacity (13). IFN-␥, after binding to its highaffinity receptor, regulates over 200 genes (7). IFN-␥ upregulates major histocompatibility complex (MHC) class I protein expression and induces MHC class II proteins on a variety of leucocytes and epithelial cells. IFN-␥ is also the major cytokine responsible for activating or regulating the phagocytic function of mononuclear cells. It also regulates the production of several immunomodulatory or proinflammatory cytokines such as interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-␣) (7).The IFN-␥ high-affinity receptor is composed of at least two subunits. IFN-␥R1 (alpha chain or CD119) is the IFN-␥ binding chain. It is encoded by a 30-kb gene located on the long arm of chromosome 6 (23), and it is expressed at moderate levels on the surfaces of nearly all cells. IFN-␥R2 (beta chain or accessory factor 1) is the signaling chain (27), and it is encoded by a gene located on chromosome 21q22.1 (8).The relationship between IFN-␥, IL-12, and TNF-␣ makes up a particularly important system, since it controls mycobacterial infections in humans (14). Recently, several mutations in some components of this system (ligands or receptors) have been described (4,11,12,(17)(18)(19)21). Patients with these mutations have similar susceptibilities to infections by atypical and nontuberculous mycobacteria (5).
MATERIALS AND METHODS
Subjects.A 5-year-old Spanish girl from consanguineous parents was referred to our hospital with disseminated infecti...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.