MHV68 latency modulates the host immune response to influenza A virus.

Murine gammaherpesvirus 68 (MHV68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. Like other herpesviruses, MHV68 causes acute infection and establishes life-long latency in the host. Recently, it has been shown that mice latently infected with MHV68 have resistance to unrelated pathogens in secondary infection models.

The linkage of innate and adaptive immune response during granulomatous development.

Granulomas represent a spectrum of inflammatory sequestration responses that may be initiated by a variety of agents, including non-infectious environmental factors and infectious microbial pathogens. Although this reaction is designed to be protective, the associated tissue injury is often responsible for a profound degree of pathology. While many of the mechanisms that sustain the development of the granuloma are enigmatic, it is accepted that the maintenance of this inflammatory process is dependent upon dynamic interactions between an inciting agent, inflammatory mediators, various immune and inflammatory cells, and structural cells of the involved tissue.

Notch system in the linkage of innate and adaptive immunity.

The lung is one of the most immunologically challenged organs and can be affected by a number of pathogens, including bacteria, virus, fungi, and parasites. The development and chronicity of pulmonary infection are determined by the early innate response to the pathogenic stimuli and are regulated at multiple levels. Initial studies have indicated that the interaction of Notch and Notch ligands plays a critical role during development, and further, the Notch system is an important bridge between APCs and T cell communication circuits.

CCR6 as a mediator of immunity in the lung and gut.

Chemokines are key mediators of leukocyte recruitment during pathogenic insult and also play a prominent role in homeostasis. While most chemokine receptors bind to multiple chemokines, CCR6 is unique in that this receptor is one of only a few that can bind only a single chemokine ligand, CCL20. CCR6 is an important receptor that is involved in regulating several aspects of mucosal immunity, including the ability to mediate the recruitment of immature dendritic cells (DCs) and mature DCs, and professional antigen presenting cells (APCs) to the sites of epithelial inflammation.

Stratification is the key: inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis.

Objective: This study examined the effectiveness of prospective stratification to identify and target high-dose glucocorticoid therapy for subjects developing lethal sepsis.

Design: Prospective, randomized, laboratory-controlled experiment.

Setting: University research laboratory.

Interferon regulatory factor 1 (IRF-1) and IRF-2 expression in breast cancer tissue microarrays.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine with potent antitumor effects, both in vitro and in vivo. The antitumor activity of IFN-gamma is mediated in part through IFN regulatory factor-1 (IRF-1) and may be blocked by IRF-2. To test our hypothesis that some tumors escape the antitumor effects of IFN-gamma by cellular changes reflected in IRF-1 and IRF-2 expression, we examined IRF-1 and IRF-2 expression in tissue microarrays (TMA) containing 187 specimens of clinically defined invasive breast carcinoma.

Localization of IFN-gamma-activated Stat1 and IFN regulatory factors 1 and 2 in breast cancer cells.

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-gamma exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-gamma signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-gamma stimulation.

The role of interferon regulatory factor-1 and interferon regulatory factor-2 in IFN-gamma growth inhibition of human breast carcinoma cell lines.

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-gamma-inducible genes. To investigate the signal transduction pathway in response to IFN-gamma in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-gamma. MDA468 growth was markedly inhibited by IFN-gamma, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction.

Copper-64-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: monitoring therapy response with microPET and magnetic resonance imaging.

Laparoscopic colectomy for curable colon cancer may result in the development of abdominal wall implants because of disseminated disease and the favorable environment of the wound site for cell implantation. Injection of disaggregated human GW39 colon cancer cells into the hamster peritoneum represents a model of tumor spillage that may occur during dissection, manipulation, resection, and extraction of tumor during surgery in the clinical setting. Using this well-established animal model, we tested the efficacy of (64)Cu-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) ((64)Cu-PTSM) in inhibiting tumor cell implantation in trocar wound sites.