Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells.

Although T cells bearing gamma delta T-cell receptors have long been known to be present in the epithelial lining of many organs, their specificity and function remain elusive. In the present study, we examined the intestinal epithelia of T-cell-receptor mutant mice, which were deficient in either gamma delta T cells or alpha beta T cells, and of normal littermates. The absence of gamma delta T cells was associated with a reduction in epithelial cell turnover and a downregulation of the expression of major histocompatibility complex class II molecules. No such effects were observed in alpha beta T-cell-deficient mice. These findings indicate that intraepithelial gamma delta T cells regulate the generation and differentiation of intestinal epithelial cells.

T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein.

Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of a local immunologic activation in the atherosclerotic plaque, but the antigen(s) involved has not yet been identified. We established T-cell clones from human atherosclerotic plaques using polyclonal mitogens as stimuli and exposed the clones to potential antigens in the presence of autologous monocytes as antigen-presenting cells. Four of the 27 CD4+ clones responded to oxidized low density lipoprotein (oxLDL) by proliferation and cytokine secretion; this response was dependent on autologous antigen-presenting cells and restricted by HLA-DR. All clones that responded to oxLDL secreted interferon gamma upon activation, but only one produced interleukin 4, suggesting that the response to oxLDL results in immune activation and inflammation but may not be a strong stimulus to antibody production. No significant response to oxLDL could be detected in CD4+ T-cell clones derived from the peripheral blood of the same individuals. Together, the present data suggest that the inflammatory infiltrate in the atherosclerotic plaque is involved in a T-cell-dependent, autoimmune response to oxLDL.

Detecção e caracterização moleculares dos paramixovírus aviários tipo 1 em materiais provenientes de aves silvestres utilizando testes para a detecção dos vírus da família viral Paramyxoviridae

As aves silvestres são importantes reservatórios de vírus que podem acometer as aves domésticas. O monitoramento da circulação viral em aves silvestres é de extrema importância para garantir a sanidade dos plantéis avícolas. O presente estudo teve como objetivo 1) comparar dois testes moleculares de RT-PCR para a detecção dos vírus da família Paramyxoviridae em aves silvestres e sinantrópicas; 2) caracterizar os vírus detectados nestas amostras. Dois testes de RT-PCR e testes específicos de RT-PCR em tempo real (RRT-PCR) para o vírus da doença de Newcastle (NDV) e o metapneumovírus aviário (aMPV) foram utilizados para comparar o limite de detecção entre as amostras. As amostras de aves silvestres foram testadas por dois testes de RT-PCR. Um pequeno fragmento da região do sítio de clivagem do gene F das amostras positivas foi sequenciado. Os testes de RT-PCR foram validados com sucesso, mas apresentaram diferenças entre os limites de detecção quando comparados aos testes específicos de RRT-PCR utilizando diferentes vírus. No total, 100 amostras de aves (suabes) foram testados pelo teste RT-PCR que apresentou um limite de detecção similar entre os diferentes agentes virais. O teste selecionado foi capaz de detectar duas amostras de aves silvestres que foram também detectadas pelo testes específico para NDV e relacionadas às amostras de NDV vacinais do genótipo II da classe II referentes aos vírus de NDV lentogênico (113RQGR ↓ L117). Nosso estudo demonstra a deficiência na biosseguridade adotada pelos sistemas avícolas por permitir a saída dos vírus vacinais para as aves silvestres

Variabilidade intratípica de HPV 16 em relação à origem étnica e HLA de uma população de alto risco para o câncer do colo do útero

A infecção por papilomavirus é a principal causa de desenvolvimento de neoplasias intraepiteliais cervicais (NIC) e câncer do colo do útero (CCU). Estudos epidemiológicos têm demonstrado que a persistência do genoma viral encontra-se associado a variantes moleculares específicas de papilomavirus humano (HPV) de alto risco. As moléculas HLA de classe II têm um importante papel na resposta imune. Associações entre HLA e CCU ou infecção por HPV tem sido demonstrado em diferentes populações. O nosso objetivo foi verificar se a variabilidade de HLA-DRB1 e DQB1 estavam associada ao CCU e NIC III em mulheres de Belém, uma população formada pelos 3 principais grupos étnicos humanos e uma área de alto risco para o CCU no Norte do Brasil. Foi investigada a existência de diferenças na distribuição de alelos HLA entre mulheres com CCU e NIC III portadoras de diferentes variantes de HPV-16 e mulheres citologicamente normais. Os genes HLA DQB1 e DRB1 foram tipados pelo método de PCR-SSO em 95 casos e 287 controles de mulheres com citologia normal atendidas em um centro de prevenção do colo do útero na mesma cidade. As variantes de HPV-16 foram tipadas por sequenciamento de um fragmento da região controladora do genoma viral (LCR). O polimorfismo na posição 350 do gene E6 foi tipado baseado em um protocolo de hibridização em pontos, para identificar a alteração na posição 350T→G. A magnitude das associações foi estimada por odds ratio (OR) e os respectivos intervalos de confiança (IC), ajustados para potenciais fatores de confusão. Uma associação positiva foi observada entre CCU e os haplótipos DRB1* 150 l-DQB1*0602, DRB1*04-DQB1*0301 e DRB1*1602-DQB1*0301. Ao contrário, DRB1*01-DQB1*0501 mostrou um efeito protetor. Os alelos DRB1*0804, DQB1*0402 apresentaram efeito protetor contra positividade por HPV. O alelo DQB1*0502 e o grupo DRB1*15 foram positivamente associados. Os nossos resultados mostram que as associações positivas de DRB1*1501 e DRB1*1602 podem ser atribuídas a variantes asiático-americanas quando comparado a variantes européias. O risco conferido a DRB1*1501 foi encontrado associado tanto a variantes E6350G quanto a variantes E6350T, entretanto, o maior efeito foi devido às variantes E6250T. A associação positiva de DRB1*1602 foi significativa somente no grupo de mulheres positivas para E6350G. Estes resultados estão de acordo com a composição étnica da população estudada bem como um maior potencial oncogênico de certas variantes. Nossos dados sugerem que a contribuição dos alelos HLA na susceptibilidade genética ao CCU difere de acordo com a distribuição das variantes de HPV em uma dada região geográfica ou grupo étnico.

Calidad de la dieta española según el índice de alimentación saludable

Objetivo: determinar la calidad de la dieta española mediante el Índice de Alimentación-Saludable (IASE) y su relación con variables geográficas y socioeconómicas. Metodología: Estudio descriptivo transversal a partir de Encuesta-Nacional-Salud-2006 (ENS-2006) Se estudiaron 29.478 personas (Mujeres = 15.019; Hombres = 14.459) que respondieron el Cuestionario de Frecuencia de Consumo (CFC). El IASE se compone de 10 variables (Cereales-derivados, Verduras-hortalizas, Frutas, Leche-derivados, Carnes, Legumbres, Embutidos-fiambres, Dulces, Refrescos-azúcar y Variedad-dieta), construidas a partir del CFC y las recomendaciones de las Guías-Alimentarias (Sociedad-Española-Nutrición-Comunitaria-2004). Categorías IASE (puntuación-máxima 100): Alimentación-saludable: > 80 puntos; Necesita-cambios: > 5.080; Poco-saludable: 50. Se realizó un análisis descriptivo, de diferencias de medias (pruebas Kruskal–Wallis y Mann–Whitney), y prueba Chi-Cuadrado, para estudiar la independencia de las variables edad, sexo, clase-social y nivel de estudios con las categorías de IASE. Resultados: El 72% del total de la muestra necesita cambios en su alimentación. La puntuación media para mujeres es 73,7 ± 10,5 y para hombres 69,9 ± 11,3 (p < 0,001). En la categoría saludable obtienen mayor porcentaje (38,8%) el grupo de edad > 65 años y las mujeres (28,3%) frente a los hombres (18,4%). Así mismo, las clases-sociales más altas (clase-I: 24,4%, clase-II: 25,0%, clase-III: 25,8%) presentan mayor índice de alimentación-saludable, (p < 0,001). Las Comunidades-Autónomas: Comunitat Valenciana (5,4%), Illes Balears (4,6%) y Andalucía (4,3%) son las que presentan mayor índice en la categoría poco-saludable. Conclusiones: El IASE es un método rápido y económico de estimación de la calidad de la dieta de la población, porque utiliza datos secundarios procedente de la ENS y de las guías-alimentarias; siendo útil en la planificación de políticas nutricionales en España.

Red supergiants around the obscured open cluster Stephenson 2

Context. Several clusters of red supergiants have been discovered in a small region of the Milky Way close to the base of the Scutum-Crux Arm and the tip of the Long Bar. Population synthesis models indicate that they must be very massive to harbour so many supergiants. Amongst these clusters, Stephenson 2, with a core grouping of 26 red supergiants, is a strong candidate to be the most massive young cluster in the Galaxy. Aims. Stephenson 2 is located close to a region where a strong over-density of red supergiants had been found. We explore the actual cluster size and its possible connection to this over-density. Methods. Taking advantage of Virtual Observatory tools, we have performed a cross-match between the DENIS, USNO-B1 and 2MASS catalogues to identify candidate obscured luminous red stars around Stephenson 2, and in a control nearby region. More than 600 infrared bright stars fulfill our colour criteria, with the vast majority having a counterpart in the I band and >400 being sufficiently bright in I to allow observation with a 4-m class telescope. We observed a subsample of ~250 stars, using the multi-object, wide-field, fibre spectrograph AF2 on the WHT telescope in La Palma, obtaining intermediate-resolution spectroscopy in the 7500–9000 Å range. We derived spectral types and luminosity classes for all these objects and measured their radial velocities. Results. Our targets turned out to be G and K supergiants, late (≥ M4) M giants, and M-type bright giants (luminosity class II) and supergiants. We found ~35 red supergiants with radial velocities similar to Stephenson 2 members, spread over the two areas surveyed. In addition, we found ~40 red supergiants with radial velocities incompatible in principle with a physical association. Conclusions. Our results show that Stephenson 2 is not an isolated cluster, but part of a huge structure likely containing hundreds of red supergiants, with radial velocities compatible with the terminal velocity at this Galactic longitude (and a distance ~6 kpc). In addition, we found evidence of several populations of massive stars at different distances along this line of sight.

Boston, Massachusetts Region 1:5,000 Color Ortho Imagery (1/2-meter Resolution), 2001

1/2-meter resolution 1:5,000 orthophoto image of the Boston region from April 2001. This datalayer is a subset (covering only the Boston region) of the Massachusetts statewide orthophoto image series available from MassGIS. It consists of 23 orthophoto quads mosaicked together (MassGIS orthophoto quad ID: 229890, 229894, 229898, 229902, 233886, 233890, 233894, 233898, 233902, 233906, 233910, 237890, 237894, 237898, 237902, 237906, 237910, 241890, 241894, 241898, 241902, 245898, 245902). These medium resolution true color images are considered the new "basemap" for the Commonwealth by MassGIS and the Executive Office of Environmental Affairs (EOEA). MassGIS/EOEA and the Massachusetts Highway Department jointly funded the project. The photography for the mainland was captured in April 2001 when deciduous trees were mostly bare and the ground was generally free of snow. The geographic extent of this dataset is the same as that of the MassGIS dataset: Boston, Massachusetts Region LIDAR First Return Elevation Data, 2002 [see cross references].

Doença celíaca num doente com síndrome poliglandular autoimune tipo III : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers

Previous cancer vaccination trials often aimed to activate CD8(+) cytotoxic T-cell (CTL) responses with short (8-10mer) peptides and targeted CD4(+) helper T cells (TH) with HLA class II-binding longer peptides (12-16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We monitored 49 patients and found strong CD8(+) T-cell responses in 63% of the patients. In addition, we unexpectedly found CD4(+) TH cell responses against at least two of the five short peptides in 61% (23/38) of the patients analyzed. The two peptides were recognized by HLA-DP4- and HLA-DR-restricted TH1 cells. Some short peptide-reactive (sp)CD4 T cells showed high functional avidity. Here, we show that a short peptide vaccine is able to activate a specific CD4(+) T-cell repertoire in many patients, facilitating a strong combined CD4(+)/CD8(+) T-cell response. Cancer Immunol Res; 4(1); 18-25. ©2015 AACR.

American state papers : documents, legislative and executive, of the Congress of the United States ... /

Nos. 1-38 of the Congressional series.

Tuning the metal-to-metal charge transfer energy of cyano-bridged dinuclear complexes

The metal-to-metal charge transfer (MMCT) transitions of a series of Class II mixed valence dinuclear complexes bearing cyano bridging ligands may be varied systematically by variations to either the hexacyanometallate(II) donor or Co-III acceptor moieties. Specifically, the new dinuclear species trans-[(LCoNCFe)-Co-14S(CN)(5)](-) (L-14S = 6-methyl-1,11-diaza-4,8-dithia- cyclotetradecane-6-amine) and trans-[(LCoNCRu)-Co-14(CN)(5)]-(L-14 = 6-methyl-1,4,8,11-tetraazacyclotetradecane-6-amine) have been prepared and their spectroscopic and electrochemical properties are compared with the relative trans-[(LCoNCFe)-Co-14(CN)(5)](-). The crystal structures of Na{trans-[(LCoNCFe)-Co-14S(CN)(5)]}.51/2H(2)O.1/2EtOH, Na{trans-[(LCoNCRu)-Co-14(CN)(5)]}.3H(2)O and Na{trans-[(LCoNCRu)-Co-14(CN)(5)]}.8H(2)O are also reported. The ensuing changes to the MMCT energy have been examined within the framework of Hush theory, and it was found that the free energy change between the redox isomers was the dominant effect in altering the energy of the MMCT transition.

T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to subsequent activation

Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappaB inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappaB inhibitor, signal phosphorylation of TCRzeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappaB determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappaB(-)CD40(-)class II+ DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to prime or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.

Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.