Intravenous immunoglobulin as a therapy for autoimmune conditions.

Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.

Machine learning application in autoimmune diseases: State of art and future prospectives.

Autoimmune diseases are a group of disorders resulting from an alteration of immune tolerance, characterized by the formation of autoantibodies and the consequent development of heterogeneous clinical manifestations. Diagnosing autoimmune diseases is often complicated, and the available prognostic tools are limited. Machine learning allows us to analyze large amounts of data and carry out complex calculations quickly and with minimal effort.

Alarmins in autoimmune diseases.

Alarmins are endogenous, constitutively expressed, chemotacting and immune activating proteins or peptides released because of non-programmed cell death (i.e. infections, trauma, etc).

A herpesvirus transactivator and cellular POU proteins extensively regulate DNA binding of the host Notch signaling protein RBP-Jκ to the virus genome.

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency requires the viral transactivator Rta to contact the host protein Jκ recombination signal-binding protein (RBP-Jκ or CSL). RBP-Jκ normally binds DNA sequence-specifically to determine the transcriptional targets of the Notch-signaling pathway, yet Notch alone cannot reactivate KSHV. We previously showed that Rta stimulates RBP-Jκ DNA binding to the viral genome.

Histone deacetylase classes I and II regulate Kaposi's sarcoma-associated herpesvirus reactivation.

In primary effusion lymphoma (PEL) cells infected with latent Kaposi's sarcoma-associated herpesvirus (KSHV), the promoter of the viral lytic switch gene, Rta, is organized into bivalent chromatin, similar to cellular developmental switch genes. Histone deacetylase (HDAC) inhibitors (HDACis) reactivate latent KSHV and dramatically remodel the viral genome topology and chromatin architecture. However, reactivation is not uniform across a population of infected cells.

The cellular peptidyl-prolyl cis/trans isomerase Pin1 regulates reactivation of Kaposi's sarcoma-associated herpesvirus from latency.

Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma and primary effusion lymphoma. KSHV-infected cells are predominantly latent, with a subset undergoing lytic reactivation. Rta is the essential lytic switch protein that reactivates virus by forming transactivation-competent complexes with the Notch effector protein RBP-Jk and promoter DNA.

Kaposi's sarcoma-associated herpesvirus Rta tetramers make high-affinity interactions with repetitive DNA elements in the Mta promoter to stimulate DNA binding of RBP-Jk/CSL.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is the etiologic agent of Kaposi's sarcoma (KS) and lymphoproliferative diseases. We previously demonstrated that the KSHV lytic switch protein Rta stimulates DNA binding of the cellular RBP-Jk/CSL protein, the nuclear component of the Notch pathway, on Rta target promoters. In the current study, we define the promoter requirements for formation of transcriptionally productive Rta/RBP-Jk/DNA complexes.

Convergence of Kaposi's sarcoma-associated herpesvirus reactivation with Epstein-Barr virus latency and cellular growth mediated by the notch signaling pathway in coinfected cells.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphoma (PEL). All PEL cell lines are infected with KSHV, and 70% are coinfected with Epstein-Barr virus (EBV). KSHV reactivation from latency requires promoter-specific transactivation by the KSHV Rta protein through interactions with RBP-Jk (CSL), the cellular DNA-binding component of the Notch signal transduction pathway.

Identification of direct transcriptional targets of the Kaposi's sarcoma-associated herpesvirus Rta lytic switch protein by conditional nuclear localization.

Lytic reactivation from latency is critical for the pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV). We previously demonstrated that the 691-amino-acid (aa) KSHV Rta transcriptional transactivator is necessary and sufficient to reactivate the virus from latency. Viral lytic cycle genes, including those expressing additional transactivators and putative oncogenes, are induced in a cascade fashion following Rta expression.

Promoter- and cell-specific transcriptional transactivation by the Kaposi's sarcoma-associated herpesvirus ORF57/Mta protein.

The Kaposi's sarcoma-associated herpesvirus (KSHV) Mta protein, encoded by open reading frame 57, is a transactivator of gene expression that is essential for productive viral replication. Previous studies have suggested both transcriptional and posttranscriptional roles for Mta, but little is known regarding Mta's transcriptional function. In this study, we demonstrate that Mta cooperates with the KSHV lytic switch protein, Rta, to reactivate KSHV from latency, but Mta has little effect on reactivation when expressed alone.

Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for specifying transactivation of a delayed-early promoter and stimulating viral reactivation.

The Kaposi's sarcoma-associated herpesvirus (KSHV) delayed-early K-bZIP promoter contains an ORF50/Rta binding site whose sequence is conserved with the ORF57 promoter. Mutation of the site in the full-length K-bZIP promoter reduced Rta-mediated transactivation by greater than 80%. The K-bZIP element contains an octamer (Oct) binding site that overlaps the Rta site and is well conserved with Oct elements found in the immediate-early promoters of herpes simplex virus type 1(HSV-1).

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta lytic switch protein functions as a tetramer.

The Kaposi's sarcoma-associated herpesvirus open reading frame 50 (ORF50) protein (called Rta), is necessary and sufficient for reactivation of the virus from latency. We previously demonstrated that a truncated mutant of ORF50 lacking its C-terminal transcriptional activation domain, called ORF50DeltaSTAD, formed mixed multimers with wild-type (WT) ORF50 and functioned as a dominant negative inhibitor of reactivation. For this report, we investigated the requirements for multimerization of ORF50/Rta in transactivation and viral reactivation.

Kaposi's Sarcoma-associated herpesvirus lytic switch protein stimulates DNA binding of RBP-Jk/CSL to activate the Notch pathway.

Kaposi's sarcoma-associated herpesvirus (KSHV) lytic switch protein, Rta, is a ligand-independent inducer of the Notch signal transduction pathway, and KSHV cannot reactivate from latency in cells null for the Notch target protein RBP-Jk. Here we show that Rta promotes DNA binding of RBP-Jk, a mechanism that is fundamentally different from that established for the RBP-Jk-activating proteins, Notch intracellular domain (NICD) and Epstein-Barr virus EBNA2. Although constitutively active RBP-Jk and NICD do not transactivate KSHV promoters independently, cotransfection of an Rta mutant lacking its transactivation domain robustly restores transcriptional activation.

Rheological and cohesive properties of hyaluronic acid.

Hyaluronic acid (HA) is a naturally occurring polysaccharide with unique biomedical applications. We have studied the cohesive and rheological properties of HA of three molecular weights (0.35 x 10(6) -1.

Differential gene expression profile of human tonsil high endothelial cells: implications for lymphocyte trafficking.

Lymphocyte recirculation is dependent on the interactions of adhesion and signaling molecules expressed on lymphocytes and their partners on high endothelial cells (HEC). Many of the events in this process have yet to be molecularly characterized. To identify novel HEC-specific proteins with potential function in the recruitment cascade, we sequenced a normalized human tonsil HEC cDNA library (generated from an inflamed tonsil) from which lymphocyte and human umbilical vein endothelial cell cDNAs had been subtracted.

Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis.

Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized.

DNA binding by Kaposi's sarcoma-associated herpesvirus lytic switch protein is necessary for transcriptional activation of two viral delayed early promoters.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus-8) establishes latent and lytic infections in both lymphoid and endothelial cells and has been associated with diseases of both cell types. The KSHV open reading frame 50 (ORF50) protein is a transcriptional activator that plays a central role in the reactivation of lytic viral replication from latency. Here we identify and characterize a DNA binding site for the ORF50 protein that is shared by the promoters of two delayed early genes (ORF57 and K-bZIP).

Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells.

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specialized microvasculature, known as high endothelial venules. There is a great deal of information available about the first steps in the homing cascade, but molecular understanding of lymphocyte transmigration through the intercellular junctions of high endothelial venules is lacking. In analyzing expressed sequence tags from a cDNA library prepared from human tonsillar high endothelial cells, we have identified a cDNA encoding a novel member of the immunoglobulin superfamily.

Importin beta can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin alpha.

The import of proteins into the nucleus is dependent on cis-acting targeting sequences, nuclear localization signals (NLSs), and members of the nuclear transport receptor (importin-beta-like) superfamily. The most extensively characterized import pathway, often termed the classical pathway, is utilized by many basic-type (lysine-rich) NLSs and requires an additional component, importin alpha, to serve as a bridge between the NLS and the import receptor importin beta. More recently, it has become clear that a variety of proteins enter the nucleus via alternative import receptors and that their NLSs bind directly to those receptors.

Multiple perspectives on nutrition education needs of low-income Hispanics.

As part of a multi-level nutrition intervention for low-income Hispanics (LIH) and the professionals and paraprofessionals who serve them, focus groups were used to 1) identify nutrition education needs and preferred means of receiving nutrition information, 2) identify the LIH's barriers/motivators to dietary behavior change, and 3) assess the feasibility of using abuelas (Hispanic grandmothers) as educators. Nine focus groups were conducted using trained, local bilingual and bicultural moderators. Low-income Hispanics' primary concerns were their children's nutritional habits and ways to prepare quick, nutritious meals and snacks.