Spirometric Values of Greek People and Comparison with ECSC and GLI Values in COPD People.

Background: During the past few years, the use of criteria introduced by Global Initiative for Chronic Obstructive Lung Disease (GOLD) is recommended for the diagnosis and classification of Chronic Obstructive Pulmonary Disease(COPD),taking into account the values of a Forced Expiratory Volume In 1 second (FEV1) and a Forced Expiratory Volume In 1 second (FEV1) to Forced Vital Capacity (FVC) ratio. In Europe, the reference values of the European Coal and Steel Community (ECSC), that were originally developed in 1993 are still used.

Aim Of The Study: The study aimed to carry out measurement of spirometric values in a healthy, non smoking Greek population, development of local equations and comparison with ECSC and Global Lung Initiative(GLI) equations, in order to see if there is a need for separate ones in everyday use.

Carboxyhemoglobin and methemoglobin levels as prognostic markers in acute pulmonary embolism.

Objectives: Carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels have been associated with a poor outcome in patients with various pathological conditions including cardiovascular diseases. Our aim was to retrospectively assess the prognostic value of arterial COHb and MetHb in patients with acute pulmonary embolism (PE).

Methods: We conducted a retrospective study of 156 patients admitted in a pulmonary clinic due to acute PE.

Cutting Edge: Selective role of ubiquitin in MHC class I antigen presentation.

The importance of ubiquitination in MHC class I-restricted Ag processing remains unclear. To address this issue, we overexpressed wild-type and dominant-negative lysineless forms of ubiquitin (Ub) in mammalian cells using an inducible vaccinia virus system. Overexpression of the lysineless Ub nearly abrogated polyubiquitination and potently inhibited epitope presentation from a cytosolic N-end rule substrate as well as endoplasmic reticulum (ER)-targeted model Ags.

Robust genital gag-specific CD8+ T-cell responses in mice upon intramuscular immunization with simian adenoviral vectors expressing HIV-1-gag.

Most studies on E1-deleted adenovirus (Ad) vectors as vaccine carriers for antigens of HIV-1 have focused on induction of central immune responses, although stimulation of mucosal immunity at the genital tract (GT), the primary port of entry of HIV-1, would also be highly desirable. In this study, different immunization protocols using chimpanzee-derived adenoviral (AdC) vectors expressing Gag of HIV-1 clade B given in heterologous prime-boost regimens were tested for induction of systemic and genital immune responses. Although i.

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine.

Effect of preexisting immunity on an adenovirus vaccine vector: in vitro neutralization assays fail to predict inhibition by antiviral antibody in vivo.

A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8(+) T cells in mice with preexisting neutralizing antibody to wild-type AdC68.

Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses.

Interactions between the herpesvirus entry mediator (HVEM) and the B- and T-lymphocyte attenuator (BTLA) inhibit B and T cell activation. HVEM-BTLA interactions are blocked by herpes simplex virus (HSV) glycoprotein D (gD) through binding of its N-terminal domain to the BTLA binding site of HVEM. In this study, we inserted viral antigens into the C-terminal domain of gD and expressed these antigens with plasmid or E1-deleted (replication-defective) adenovirus vectors.

Recombinant adeno-associated virus vectors induce functionally impaired transgene product-specific CD8+ T cells in mice.

Recombinant adeno-associated virus (rAAV) vectors were used in human trials as carriers of vaccines for HIV-1 after encouraging preclinical results. However, the clinical trials yielded disappointing results. Here we demonstrated that in mice, rAAV vectors expressing the gene encoding HIV-1 gag stimulated gag-specific CD8(+) T cells, but these T cells failed to expand after a booster immunization with a replication-defective adenoviral (Ad) vector also expressing gag.

Multiple immunizations with adenovirus and MVA vectors improve CD8+ T cell functionality and mucosal homing.

Recombinant adenovirus vectors and MVA vectors were used in prime boost vaccine regimens to address the impact of repeated immunizations on transgene product-specific CD8(+) T cell frequencies, phenotypes, function, and localization. We show that a regimen with three immunizations incorporating MVA, human adenovirus serotype 5 and chimpanzee-derived adenoviruses serotype 68 or 7 yields high transgene product-specific CD8(+) T cell frequencies in spleen, blood, lymph nodes, and peritoneal lavage. Furthermore, upon triple immunization increased frequencies of transgene-specific T cells were measured at mucosal sites such as mesenteric lymph nodes, intestinal epithelium, and Peyer's patches.

Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines.

CD8(+) T cell-numbers rapidly expand and then contract after exposure to their cognate antigen. Here we show that the sustained frequencies of transgene product-specific CD8(+) T cells elicited by replication-defective adenovirus vectors are linked to persistence of low levels of transcriptionally active adenovirus vector genomes at the site of inoculation, in liver, and lymphatic tissues. Continuously produced small amounts of antigen maintain fully active effector CD8(+) T cells, while also allowing for their differentiation into central memory cells.

Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors.

In this study we compared a prime-boost regimen with two serologically distinct replication-defective adenovirus (Ad) vectors derived from chimpanzee serotypes C68 and C1 expressing Gag, Pol, gp140, and Nef of human immunodeficiency virus type 1 with a regimen in which replication-defective Ad vectors of the human serotype 5 (AdHu5) were given twice. Experiments were conducted in rhesus macaques that had or had not been preexposed to antigens of AdHu5. There was no significant difference in T-cell responses tested from peripheral blood of the different groups, although responses were overall highest in nonpreexposed animals immunized with the chimpanzee Ad vectors.

A CD46-binding chimpanzee adenovirus vector as a vaccine carrier.

A replication-defective chimeric vector based on the chimpanzee adenovirus serotype C1 was developed and tested as a vaccine carrier in mice. The AdC1 virus is closely related to human adenoviruses of subgroup B2 and uses CD46 for cell attachment. To overcome poor growth of E1-deleted AdC1 vectors on cell lines that provide the E1 of adenovirus of the human serotype 5 (AdHu5) virus in trans, the inverted terminal repeats and some of the early genes of AdC1 were replaced with those from AdC5, a chimpanzee origin adenovirus of subfamily E.

Chimpanzee-origin adenovirus vectors as vaccine carriers.

Vaccines based on replication-defective adenoviral vectors are being developed for infectious agents and tumor-associated antigens. Early work focused on vaccines derived from a common human serotype of adenovirus, that is, adenovirus of the serotype 5 (AdHu5). Neutralizing antibodies against AdHu5 virus, present in a large percentage of the human population, dampen the efficacy of vaccines based on this carrier.

Adenoviruses as vaccine vectors.

Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles. They are attractive vaccine vectors as they induce both innate and adaptive immune responses in mammalian hosts. Currently, adenovirus vectors are being tested as subunit vaccine systems for numerous infectious agents ranging from malaria to HIV-1.

Vaccinia virus as a tool for immunologic studies.

Studies that involve antigen processing and presentation often require de novo biosynthesis of the antigen both in vitro and in vivo. Additionally, biosynthesis of the antigen or engineered variants within the antigen-presenting cells is usually simpler than providing purified recombinant proteins from bacteria, yeast, or insect cells. For these purposes, recombinant vaccinia virus-based expression has several advantages over other expression systems employed in the field.

The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.

Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen (HLA)-identical allogeneic stem cell transplantation (SCT). To understand the basis of alloimmune responses against minor H antigens, identification of minor H peptides and their antigenicity-determining mechanisms is essential. Here we report the identification of HA-3 and its encoding gene.

The function of the p190 Rho GTPase-activating protein is controlled by its N-terminal GTP binding domain.

p190 is a GTPase-activating protein (GAP) for the Rho family of GTPases. The GAP domain of p190 is at the C terminus of the protein. At its N terminus, p190 contains a GTP binding domain of unknown significance.

Distinct cellular effects and interactions of the Rho-family GTPase TC10.

Background: Rho-family GTPases have central roles in cytoskeletal organization, proliferation, differentiation and apoptosis. Multiple factors possessing overlapping specificities for Rho GTPases have been identified. The Rho GTPases Cdc42 and Rac share many regulators and effectors, yet produce different phenotypes when expressed as gain-of-function mutants in cells.