Biomedical subjects

Yuping Deng

Publications and source records attributed to Yuping Deng.

7 recordsLinked to original sources

PubMed2005

Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125.

OBJECTIVES: CA125 expresses specific oligosaccharides that can inhibit the cytotoxicity of human natural killer (NK) cells. The current study was undertaken to determine the ability of CA125 to modulate NK cell-mediated cytotoxicity. METHODS: CA125 was isolated from OVCAR-3 cells and its purity was determined by ELISA and ultra-sensitive mass spectrometric analysis. Peripheral blood-derived NK were treated with CA125 and standard cytotoxicity assays were performed using 51Cr-labeled K562 cells as targets. The expression of cell surface and intracellular markers on NK cells was determined by either flow cytometry or Western blot analysis. RESULTS: NK cells incubated with CA125 for 72 h exhibited a 50-70% decrease in the lysis of K562 targets. Incubation with CA125 for 4 h and 24 h had no effect on NK-mediated cytolysis. Inhibition of NK function was observed at CA125 concentrations (10,000-100,000 U/ml) that are expected to be significantly lower than those observed in the tumor microenvironment. Co-stimulation with IL-2 did not abrogate the NK inhibitory response of CA125. CA125 did not reduce proliferation or induce apoptosis of NK cells and alter the expression of p56lck, phospholipase Cgamma1, ZAP70, or CD3zeta. CA125 did, however, induce major downregulation of CD16 and minor decrease in expression of CD94/NKG2A. CONCLUSIONS: Our ongoing research and recent work performed by other laboratories highlights the potential physiologic role of this mucin. Based on the data presented here, it is likely that the tumor-derived CA125 acts as a suppressor of the immune response that is directed against the ovarian tumors.

CA-125 Antigen↗

PubMed2005

Proteomics for biodefense applications: progress and opportunities.

The increasing threat of bioterrorism and continued emergence of new infectious diseases has driven a major resurgence in biomedical research efforts to develop improved treatments, diagnostics and vaccines, as well as increase the fundamental understanding of the host immune response to infectious agents. The availability of multiple mass spectrometry platforms combined with multidimensional separation technologies and microbial genomic databases provides an unprecedented opportunity to develop these much needed resources. An overview of current proteomic strategies applied to microbes and viruses considered potential bioterrorism agents is presented. The emerging area of immunoproteomics as applied to the development of new vaccine targets is also summarized. These powerful research approaches can generate a multitude of potential new protein targets; however, translating these proteomic discoveries to useful counter-bioterrorism products will require large collaborative research efforts across multiple basic science and clinical disciplines. A translational proteomic research paradigm illustrating this approach using influenza virus as an example is discussed.

Adult↗

PubMed2004

Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly.

The objective of this study was to analyze the changes in the type 1 T cell response, including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-related decline in type 1 T cell response, shown by the decline in the frequency of IFN-gamma-secreting memory T cells specific for influenza (IFN-gamma+ ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-gamma+ ISMT was accompanied by a reduced level of IFN-gamma secretion per cell in elderly subjects. Tetramer staining, combined with IFN-gamma ELISPOT, indicated that the decline in IFN-gamma+, influenza M1-peptide-specific T cells was not due to attrition of the T cell repertoire, but, rather, to the functional loss of ISMT with age. In addition, the decline in type 1 T cell response was not due to an increase in Th2 response or defects in APCs from the elderly. The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly. Compared with young subjects, frail elderly subjects also exhibited a blunted and somewhat delayed type 1 T cell response to influenza vaccination, which correlated positively with the reduced IgG1 subtype and the total Ab response. Taken together, these data demonstrate that there is a decline in the type 1 T cell response to influenza with age that may help explain the age-related decline in vaccine efficacy and the increases in influenza morbidity and mortality.

Adult↗

PubMed2003

Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA.

Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.

Adult↗

PubMed2003

Diverse effects of nanosecond pulsed electric fields on cells and tissues.

The application of pulsed electric fields to cells is extended to include nonthermal pulses with shorter durations (10-300 ns), higher electric fields (< or =350 kV/cm), higher power (gigawatts), and distinct effects (nsPEF) compared to classical electroporation. Here we define effects and explore potential application for nsPEF in biology and medicine. As the pulse duration is decreased below the plasma membrane charging time constant, plasma membrane effects decrease and intracellular effects predominate. NsPEFs induced apoptosis and caspase activation that was calcium-dependent (Jurkat cells) and calcium-independent (HL-60 and Jurkat cells). In mouse B10-2 fibrosarcoma tumors, nsPEFs induced caspase activation and DNA fragmentation ex vivo, and reduced tumor size in vivo. With conditions below thresholds for classical electroporation and apoptosis, nsPEF induced calcium release from intracellular stores and subsequent calcium influx through store-operated channels in the plasma membrane that mimicked purinergic receptor-mediated calcium mobilization. When nsPEF were applied after classical electroporation pulses, GFP reporter gene expression was enhanced above that observed for classical electroporation. These findings indicate that nsPEF extend classical electroporation to include events that primarily affect intracellular structures and functions. Potential applications for nsPEF include inducing apoptosis in cells and tumors, probing signal transduction mechanisms that determine cell fate, and enhancing gene expression.

Animals↗

PubMed2003

Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland.

To better understand the immunological mechanisms that permit prolonged shedding of murine cytomegalovirus (MCMV) from the salivary gland, the phenotypic and functional characteristics of leukocytes infiltrating the submaxillary gland (SMG) were analyzed in infected BALB/c mice. A robust innate immune response, comprised of CD11c+ major histocompatibility complex class II+ CD11b- CD8alpha+ dendritic cells and gamma/delta T-cell receptor-bearing CD3+ T cells was prominent through at least 28 days postinfection. Concurrently, a dramatic increase in pan-NK (DX5+) CD3+ and CD8+ T cells was observed, while CD4+ T cells, known to be essential for viral clearance from this tissue, increased slightly. The expression particularly of gamma interferon but also of interleukin-10 and CC chemokines was extraordinarily high in the SMG in response to MCMV infection. The gamma interferon was produced primarily by CD4+ and CD8+ T lymphocytes and DX5+ CD3+ T cells. The SMG CD8+ T cells were highly cytolytic ex vivo, and a significant proportion of these cells were specific to an immunodominant MCMV peptide. These peptide-specific clones were not exhausted by the presence of high virus titers, which persisted in the SMG despite the strength of the cell-mediated responses. In contrast, MCMV replication was efficiently cleared from the draining cervical and periglandular lymph nodes, a tissue displaying a substantially weaker antiviral response. Our data indicated that vigorous innate and acquired immune responses are elicited, activated, and retained in response to mucosal inflammation from persistent MCMV infection of the submaxillary gland.

3T3 Cells↗

PubMedDate not supplied

Neuraminidase inhibitors reduce nitric oxide production in influenza virus-infected and gamma interferon-activated RAW 264.7 macrophages.

The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by macrophages, which abundantly generate a free radical, nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors (NIs) restrict influenza virus replication but whether they can suppress NO production within macrophages is unknown. RAW 264.7 macrophages were exposed to interferon-gamma (IFN-gamma), live influenza (A/PR/8/34) or a combination of both and were treated with NIs (oseltamivir or zanamivir). Results revealed that the drugs reduced a synergy between influenza and IFN-gamma in NO synthesis within the cells at all of the used concentrations (0.01, 0.1, 1 microg/ml). In contrast to zanamivir, this effect occurred in a concentration-dependent manner with oseltamivir treatment. On the other hand, all concentrations of zanamivir significantly suppressed NO production in comparison to that upon the combined exposure only (p < 0.05). Both compounds also considerably decreased NO generation in the IFN-gamma-stimulated macrophages, and zanamivir in the influenza-infected cells as well. However, neither of the drugs inhibited iNOS mRNA expression in the cells containing these stimulants. Additionally, the data indicate that a prodrug oseltamivir can be activated in vitro within the macrophage cultures. These findings are important for designing treatment approaches to limit pulmonary inflammation during influenza infection.

Animals↗